Oncology Research 25(8) Abstracts

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Oncology Research, Vol. 25, pp. 1215-1222, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14791715355957
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Upregulated miR-9-3p Promotes Cell Growth and Inhibits Apoptosis in Medullary Thyroid Carcinoma by Targeting BLCAP

Yangjing Chen, Shaoqiang Zhang, Ruimin Zhao, Qian Zhao, and Ting Zhang

Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China

Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer derived from parafollicular C cells in the thyroid gland. It has great interest as a research focus because of its unusual genetic, clinical, and prognostic characteristics. However, the pathogenesis in MTC is not completely clear. We investigated the role of miR-9-3p and bladder cancer-associated protein (BLCAP) in MTC TT cells. First, miR-9-3p expression was upregulated in human MTC tissues and TT cells and compared to the control by RT-PCR. Flow cytometric analysis indicated that the cell cycle progression in TT cells was significantly inhibited by the miR-9-3p inhibitor but was increased by the miR-9-3p mimic. On the contrary, the apoptosis of TT cells was significantly increased by the miR-9-3p inhibitor and suppressed by the miR-9-3p mimic. A similar change pattern was observed in the expression of apoptosis-regulated protein caspase 3 induced by the miR-9-3p mimic or inhibitor in TT cells. We then identified that BLCAP is a target of miR-9-3p by bioinformatic prediction and luciferase reporter assay. The expression of BLCAP was also significantly downregulated by the miR-9-3p mimic while being upregulated by the miR-9-3p inhibitor in TT cells. Furthermore, we confirmed that the inhibited apoptosis of TT cells induced by the miR-9-3p mimic was enhanced by BLCAP overexpression. The levels of apoptosis were strongly decreased by BLCAP silencing in TT cells, which were not further influenced by the miR-9-3p inhibitor. In summary, upregulated miR-9-3p has a positive role in human MTC progression by regulating the growth and apoptosis of cancer cells via targeting BLCAP. This might represent a possible diagnosis or therapeutic target for MTC.

Key words: Medullary thyroid carcinoma (MTC); miR-9-3p; Bladder cancer-associated protein (BLCAP); Cell growth; Apoptosis

Address correspondence to Shaoqiang Zhang, Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an 710061, Shaanxi, P.R. China. Tel: +86-029-85323965; Fax: +86-029-85323965; E-mail address: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1223-1229, 2017
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DOI: https://doi.org/10.3727/096504017X14876245096439
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Polymorphic Variations Associated With Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients

Valentina K. Todorova,* Issam Makhoul,† Ishwori Dhakal,‡ Jeanne Wei,§ Annjanette Stone,¶ Weleetka Carter,¶ Aaron Owen,* and V. Suzanne Klimberg*

*Division of Breast Surgical Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
†Division of Medical Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
‡Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
§Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
¶Pharmacogenomics Analysis Laboratory, Research and Development Service, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA

Doxorubicin (DOX) is a commonly used antineoplastic agent for the treatment of various malignancies, and its use is associated with unpredictable cardiotoxicity. Susceptibility to DOX cardiotoxicity is largely patient dependent, suggesting genetic predisposition. We have previously found that individual sensitivity to DOX cardiotoxicity was associated with differential expression of genes implicated in inflammatory response and immune trafficking, which was consistent with the increasing number of reports highlighting the important role of human leukocyte antigen (HLA) complex polymorphism in hypersensitivity to drug toxicity. This pilot study aimed to investigate DNA from patients treated with DOX-based chemotherapy for breast cancer and to correlate the results with the risk for DOX-associated cardiotoxicity. We have identified 18 SNPs in nine genes in the HLA region (NFKBIL1, TNF-α, ATP6V1G2-DDX39B, MSH5, MICA, LTA, BAT1, and NOTCH4) and in the psoriasis susceptibility region of HLA-C as potential candidates for association with DOX cardiotoxicity. These results, albeit preliminary and involving a small number of patients, are consistent with reports showing the presence of susceptibility loci within the HLA gene region for several inflammatory and autoimmune diseases, and with our previous findings indicating that the increased sensitivity to DOX cardiotoxicity was associated with dysregulation of genes implicated both in inflammation and autoimmune disorders.

Key words: Doxorubicin (DOX); Cardiotoxicity; Genotyping; Breast cancer

Address correspondence to Valentina K. Todorova, Division of Medical Oncology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, USA. Tel: +501-686-8511; Fax: +501-686-6342; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1231-1243, 2017
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DOI: https://doi.org/10.3727/096504017X14850134190255
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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MicroRNA-148a Acts as a Tumor Suppressor in Osteosarcoma via Targeting Rho-Associated Coiled-Coil Kinase

HaiYan Yang,*† ZhiGang Peng,† ZhenZhen Da,* Xin Li,‡ YeXiao Cheng,* BinBin Tan,§ Xin Xiang,¶ HaiPing Zheng,† Yan Li,* LanHua Chen,* Ning Mo,† XueXin Yan,† Xiaolin Li,* and XiaoHua Hu†

*Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
†Department of Oncology, First Affiliated Hospital of Guangxi Medical, Nanning, Guangxi, P.R. China
‡Department of Digestion, Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P.R. China
§Department of Blood Transfusion, First Affiliated Hospital of Guangxi Medical, Nanning, Guangxi, P.R. China
¶Department of Nephrology, Affiliated National Hospital of Guangxi Medical University, Nanning, Guangxi, P.R. China

MicroRNAs (miRs) have been demonstrated to be involved in the development and progression of osteosarcoma (OS), but the molecular mechanism still remains to be fully investigated. The present study investigated the function of miR-148a in OS, as well as its underlying mechanism. Our data showed that miR-148a was significantly downregulated in OS tissues compared to their matched adjacent normal tissues, and also in OS cell lines compared to normal human osteoblast cells. Low expression of miR-148a was significantly associated with tumor progression and a poor prognosis for OS patients. Rho-associated coiled-coil kinase 1 (ROCK1) was then identified as a target of miR-148a in Saos-2 and U2OS cells, and the expression of ROCK1 was significantly increased in OS tissues and cell lines. Moreover, the protein expression of ROCK1 was markedly reduced in miR-148a-overexpressing Saos-2 and U2OS cells, but significantly increased in miR-148a-downregulated Saos-2 and U2OS cells. Further investigation indicated that miR-148a had a suppressive effect on the proliferative, migratory, and invasive capacities of Saos-2 and U2OS cells. Moreover, overexpression of ROCK1 attenuated the inhibitory effects of miR-148a upregulation on the malignant phenotypes of Saos-2 and U2OS cells. In addition, overexpression of miR-148a significantly inhibited the tumor growth of U2OS cells in nude mice. Taken together, these data demonstrate that miR-148a acts as a tumor suppressor in OS, at least partly, via targeting ROCK1. Therefore, the miR-148a/ROCK1 axis may become a potential therapeutic target for OS.

Key words: Osteosarcoma; MicroRNAs (miRs); Rho-associated coiled-coil kinase 1 (ROCK1); Tumor suppressor

Address correspondence to Professor Xiaolin Li, Department of Hematology, Xiangya Hospital of Centre South University, 87 Xiangya Road, Changsha, Hunan 410008, P.R. China. Tel: +86-371-84327332; Fax: +86-371-84327332; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Professor Xiaohua Hu, Department of Oncology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi 530021, P.R. China. Tel: +86-771-5312980; Fax: +86-771-5312980; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1245-1252, 2017
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DOI: https://doi.org/10.3727/096504017X14850164661097
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Three Combined Treatments, a Novel HDAC Inhibitor OBP-801/YM753, 5-Fluorouracil, and Paclitaxel, Induce G2 Phase Arrest Through the p38 Pathway in Human Ovarian Cancer Cells

Makoto Akiyama,*† Yoshihiro Sowa,* Tomoyuki Taniguchi,* Motoki Watanabe,* Shingo Yogosawa,‡ Jo Kitawaki,† and Toshiyuki Sakai*

*Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan
†Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, Japan
‡Department of Public Health and Environmental Medicine, The Jikei University School of Medicine, Nishi-Shimbashi, Minato-ku, Tokyo, Japan

Ovarian cancer is the most lethal disease among gynecological malignancies. More effective therapy is required to counter high recurrence rates and chemotherapy resistance. We investigated the efficacy and molecular mechanisms of three combined treatments (TCTs)—a novel histone deacetylase (HDAC) inhibitor OBP-801/YM753, 5-fluorouracil (5-FU), and paclitaxel (PTX)—in human ovarian cancer SKOV-3 and OVCAR-3 cells. The inhibition of cell growth was stronger with TCTs than with each single agent and with two combined treatments. The TCTs significantly induce G2 phase arrest in both cell lines. We then analyzed the molecular mechanisms and found that the TCTs increased the phosphorylation of p38 (Thr180/Tyr182), decreased the expression of CDC25C, and increased the phosphorylation of CDC2 (Tyr15), an inactive form of CDC2. To examine the responsibilities of the p38 pathway for G2 phase arrest induced by the TCTs, we employed the p38 inhibitor SB203580. SB203580 inhibited G2 phase arrest, suppression of CDC25C, and phosphorylation of CDC2 (Tyr15) induced by the TCTs. These results suggest that the TCTs can induce G2 phase arrest through activation of the p38 signaling pathway. We therefore believe that this combination is promising as a novel therapeutic strategy against ovarian cancer.

Key words: Histone deacetylase (HDAC) inhibitor; 5-Fluorouracil (5-FU); Paclitaxel (PTX); G2 phase arrest; p38; Ovarian cancer

Address correspondence to Yoshihiro Sowa, Department of Molecular-Targeting Cancer Prevention, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1253-1259, 2017
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DOI: https://doi.org/10.3727/096504017X14854310794561
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Knockdown of TRIM44 Inhibits the Proliferation and Invasion in Prostate Cancer Cells

Yuying Tan,* Hanxin Yao,† Jinghai Hu,‡ and Lingyun Liu§

*Department of Echocardiography, First Hospital of Jilin University, Changchun, Jilin, P.R. China
†Department of Clinical Laboratory, First Hospital of Jilin University, Changchun, Jilin, P.R. China
‡Department of Urology, First Hospital of Jilin University, Changchun, Jilin, P.R. China
§Department of Andrology, First Hospital of Jilin University, Changchun, Jilin, P.R. China

Tripartite motif 44 (TRIM44), a member of the TRIM protein family, has been shown to play a role in tumor development and progression. However, the potential involvement of TRIM44 in prostate cancer has not been fully explored. Therefore, in the present study, we analyzed the expression of TRIM44 in prostate cancer and assessed the role of TRIM44 in the progression of prostate cancer. Our results showed that the expression of TRIM44 was significantly upregulated in human prostate cancer cell lines. In addition, knockdown of TRIM44 significantly inhibited the proliferation, migration, and invasion of prostate cancer cells in vitro, as well as attenuated the tumor growth in vivo. Mechanistic studies showed that knockdown of TRIM44 significantly reduced the levels of phosphorylated PI3K and Akt in PC-3 cells. In conclusion, this study provided evidence that knockdown of TRIM44 inhibited proliferation and invasion in prostate cancer cells, at least in part, through the inactivation of the PI3K/Akt signaling pathway. These results suggest that TRIM44 may be a potential therapeutic target for the treatment of prostate cancer.

Key words: Tripartite motif 44 (TRIM44); Prostate cancer; Invasion; PI3K/Akt pathway

Address correspondence to Lingyun Liu, Department of Andrology, First Hospital of Jilin University, No. 71 Xinmin Street, Changchun, 130021 Jilin, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1261-1267, 2017
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DOI: https://doi.org/10.3727/096504017X14871164924588
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Knockdown of FOXK1 Suppresses Proliferation, Migration, and Invasion in Prostate Cancer Cells

Fang Chen,*1 Wei Xiong,*†1 Ke Dou,‡ and Qing Ran*

*Organ Transplantation Center, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, Chengdu, P.R. China
†Department of Urology, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, Chengdu, P.R. China
‡The East Ward, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, Chengdu, P.R. China

Forkhead box K1 (FOXK1) is a member of the FOX transcription factor family and plays an important role in the development of several tumors. However, the role of FOXK1 in the progression of prostate cancer remains unknown. Thus, the objectives of this study were to detect the expression of FOXK1 in prostate cancer and to examine its role in prostate cancer cells. We found that the expression of FOXK1 at both the mRNA and protein levels was significantly upregulated in human prostate cancer cell lines. In addition, the downregulation of FOXK1 obviously inhibited the cell proliferation of prostate cancer cells in vitro and attenuated tumor growth in a xenograft model in vivo. Furthermore, knockdown of FOXK1 suppressed the migration and invasion of prostate cancer cells, and prevented the EMT phenotype through upregulating the expression of E-cadherin, as well as downregulating the expression of N-cadherin in prostate cancer cells. Mechanistically, knockdown of FOXK1 efficiently downregulated the expression levels of β-catenin, c-myc, and cyclin D1 in PC-3 cells. Overall, our results demonstrated that knockdown of FOXK1 inhibited the proliferation and metastasis of prostate cancer, at least in part, through suppressing the Wnt/β-catenin signaling pathway. Therefore, these results suggest that FOXK1 may be a potential therapeutic target for human prostate cancer.

Key words: Forkhead box K1 (FOXK1); Prostate cancer; Proliferation; Invasion

1These authors provided equal contribution to this work.
Address correspondence to Qing Ran, Organ Transplantation Center, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, No. 32 Yihuan Road, Chengdu 610072, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1269-1282, 2017
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DOI: https://doi.org/10.3727/096504017X14850151453092
E-ISSN 1555-3906
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MicroRNA-133b Inhibits Proliferation, Cellular Migration, and Invasion via Targeting LASP1 in Hepatocarcinoma Cells

Hui Li,* Zhigang Xiang,* Yan Liu,* Bin Xu,* and Jianzhou Tang†

*Research Center of Translational Medicine, School of Medicine, Da Tian Wan Campus of Jishou University, Jishou, Hunan, P.R. China
†Department of Biotechnology and Environmental Science, Changsha University, Changsha, Hunan, P.R. China

MicroRNAs (miRs), a class of small noncoding RNAs, are key gene regulators through inducing translational repression or degradation of their target genes. However, the regulatory mechanism of miR-133b underlying hepatocellular carcinoma (HCC) growth and metastasis remains largely unclear. Here we found that miR-133b was significantly downregulated in HCC tissues and cell lines. Moreover, low miR-133b levels were significantly associated with the malignant progression of HCC. LASP1, upregulated in HCC tissues and cell lines, was then identified as a novel target of miR-133b in HCC HepG2 and Hep3B cells. Moreover, the increased expression of LASP1 was associated with HCC progression. An in vitro study showed that overexpression of miR-133b inhibited the proliferation, migration, and invasion of HepG2 and Hep3B cells. Similarly, knockdown of LASP1 reduced HepG2 and Hep3B cell proliferation, migration, and invasion. Furthermore, overexpression of LASP1 attenuated the suppressive effect of miR-133b on the malignant phenotypes of HepG2 and Hep3B cells, suggesting that miR-133b may inhibit HCC growth and metastasis via targeting LASP1. In addition, overexpression of miR-133b inhibits tumor growth of HepG2 and Hep3B cells in vivo. Therefore, the miR-133b/LASP1 axis may become a potential target for the treatment of HCC.

Key words: Hepatocellular carcinoma (HCC); MicroRNAs (miRs); LIM and SH3 protein 1 (LASP1); Growth; Metastasis

Address correspondence to Professor Jianzhou Tang, Department of Biotechnology and Environmental Science, Changsha University, 98 Hongshan Road, Changsha, Hunan 410003, P.R. China. Tel: +86-731-84261506; Fax: +86-731-84261506; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1283-1295, 2017
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DOI: https://doi.org/10.3727/096504017X14883245308282
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Inhibitors of PI3K/ERK1/2/p38 MAPK Show Preferential Activity Against Endocrine-Resistant Breast Cancer Cells

Maitham A. Khajah, Princy M. Mathew, and Yunus A. Luqmani

Faculty of Pharmacy, Kuwait University, Safat, Kuwait

Current mainstream pharmacological options for the treatment of endocrine-resistant breast cancer have limitations in terms of their side effect profile and lack of discrimination between normal and cancer cells. In the current study, we assessed the responses of normal breast epithelial cells MCF10A, estrogen receptorpositive (ER+) MCF-7, and ER-silenced pII breast cancer cells to inhibitors (either individually or in combination) of downstream signaling molecules. The expression/activity of ERK1/2, p38 MAPK, and Akt was determined by Western blotting. Cell proliferation, motility, and invasion were determined using MTT, wound healing, and Matrigel assays, respectively. Morphological changes in response to variation in external pH were assessed by light microscopy. Our results demonstrated that the inhibitors of ERK1/2 (PD0325901), p38 MAPK (SB203580), and PI3K (LY294002) preferentially reduce breast cancer cell proliferation. In pII cells, they also reduced motility, invasion, and bleb formation induced by alkaline conditions. Combination treatment with lower concentrations of inhibitors was significantly more effective than single agents and was more effective against the cancer cell lines than the normal MCF10A. In contrast, the commonly used cytotoxic agent paclitaxel did not sufficiently discriminate between the MCF10A and the cancer cells. We concluded that combination therapy using ERK1/2 inhibitor and either p38 MAPK or PI3K inhibitor may provide a greater therapeutic benefit in treating breast cancer by specifically targeting cancer cells with lower doses of each drug than needed individually, potentially reducing unwanted side effects.

Key words: Breast cancer; Endocrine resistance; pH; Invasion; ERK1/2; p38 MAPK; Akt

Address correspondence to Maitham A. Khajah, Faculty of Pharmacy, Kuwait University, Safat 13110, Kuwait. Tel: (965) 24636034; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1297-1304, 2017
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DOI: https://doi.org/10.3727/096504017X14873430389189
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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MicroRNA-520b Suppresses Proliferation, Migration, and Invasion of Spinal Osteosarcoma Cells via Downregulation of Frizzled-8

Jin Wang,* Wenquan Pang,* Zhenbai Zuo,* Wenyan Zhang,* and Weidong He†

*Department of Spinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China
†Department of Nutriology, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China

Spinal osteosarcoma (OS) is a malignant tumor that has a poor outcome. MicroRNA-520b (miR-520b) acts as a cancer suppressor in various types of cancer. Because of the limited amount of literature on OS, we aimed to identify the role of miR-520b in OS. The miR-520b level in clinical spinal OS tissues and adjacent nontumor tissues as well as in cell lines was assessed. The effect of miR-520b on cell proliferation, migration, invasion, and frizzled-8 (FZD8) degradation were all evaluated. Alterations of key proteins involved in the Wnt/β-catenin pathway were assessed by Western blot analysis. In the present study, miR-520b was downregulated in human spinal OS tissues and OS cell lines (p < 0.01 or p < 0.001). Overexpression of miR-520b inhibited cell proliferation (p < 0.01 or p < 0.001), migration (p < 0.01), and invasion (p < 0.01). FZD8 expression was negatively regulated by infection with a lentivirus vector carrying an miR-520b precursor in dose- and time-dependent manners. In OS tissues, miR-520b was inversely correlated with FZD8 expression. FZD8 was upregulated in human spinal OS tissues and cell lines. Finally, miR-520b inactivated the Wnt/β-catenin pathway through downregulation of FZD8. miR-520b inhibited cell proliferation, migration, and invasion through inactivating the Wnt/β-catenin pathway by downregulation of FZD8, providing a novel therapeutic target for spinal OS.

Key words: miR-520b; Spinal osteosarcoma (OS); Frizzled-8; Wnt/β-catenin pathway

Address correspondence to Weidong He, Department of Nutriology, The Affiliated Hospital of Qingdao University, No. 1677 Wutaishan Road, Huangdao District, Qingdao 266555, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1305-1316, 2017
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DOI: https://doi.org/10.3727/096504017X14850182723737
E-ISSN 1555-3906
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Long Noncoding RNA GAS5 Inhibits Tumorigenesis and Enhances Radiosensitivity by Suppressing miR-135b Expression in Non-Small Cell Lung Cancer

Yingbo Xue, Tingting Ni, Ying Jiang, and Yong Li

Department of Oncology, Guizhou Provincial People’s Hospital, Guiyang, P.R. China

Growth arrest-specific transcript 5 (GAS5) has been demonstrated to correlate with clinicopathological characteristics and serve as a tumor suppressor in non-small cell lung cancer (NSCLC). However, the underlying mechanism of the competing endogenous RNA (ceRNA) regulatory network involving GAS5 in NSCLC remains to be elucidated. In this study, qRT-PCR results showed that GAS5 was downregulated and miR-135b was upregulated in NSCLC tissues and cells. The expressions of GAS5 and miR-135b changed inversely in response to irradiation. Gain-of-function experiments revealed that GAS5 overexpression and miR-135b downregulation significantly suppressed tumorigenesis by repressing cell proliferation and invasion, and enhanced the radiosensitivity of NSCLC cells by reducing colony formation rates. Luciferase reporter assay confirmed that GAS5 could directly target miR-135b and negatively regulate its expression. Moreover, rescue experiments demonstrated that miR-135b upregulation markedly abolished GAS5 overexpression-induced tumorigenesis inhibition and radiosensitivity improvement. Furthermore, xenograft model analysis validated that GAS5 overexpression suppressed tumor growth and improved radiosensitivity of NSCLC cells in vivo. Taken together, GAS5 inhibits tumorigenesis and enhances radiosensitivity by suppressing miR-135b expression in NSCLC cells, deepening our understanding of the mechanism of miRNA–lncRNA interaction and providing a novel therapeutic strategy for NSCLC.

Key words: Non-small cell lung cancer (NSCLC); Growth arrest-specific transcript 5 (GAS5); Tumorigenesis; Radiosensitivity; miR-135b

Address correspondence to Yingbo Xue, Department of Oncology, Guizhou Provincial People’s Hospital, No. 83 Zhongshan East Road, Guiyang 550002, P.R. China. Tel: +86-0851-85601796; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1317-1327, 2017
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DOI: https://doi.org/10.3727/096504017X14874323871217
E-ISSN 1555-3906
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Overexpression of MicroRNA-216a Suppresses Proliferation, Migration, and Invasion of Glioma Cells by Targeting Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5

Junfeng Zhang,*1 Kun Xu,†1 Lili Shi,* Li Zhang,* Zhaohua Zhao,* Hao Xu,* Fei Liang,* Hongbo Li,* Yan Zhao,* Xi Xu,* and Yingfang Tian‡

*Department of Human Anatomy, Xi’an Medical University, Xi’an, Shaanxi, P.R. China
†Department of Ophthalmology, The No.1 Hospital of Xi’an, Xi’an, Shaanxi, P.R. China
‡College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi, P.R. China

Increasing studies have suggested that microRNAs (miRNAs) are involved in the development of gliomas. MicroRNA-216a has been reported to be a tumor-associated miRNA in many types of cancer, either as an oncogene or as a tumor suppressor. However, little is known about the function of miR-216a in gliomas. The present study was designed to explore the potential role of miR-216a in gliomas. We found that miR-216a was significantly decreased in glioma tissues and cell lines. Overexpression of miR-216a significantly suppressed the proliferation, migration, and invasion of glioma cells. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) was identified as a target gene of miR-216a in glioma cells by bioinformatics analysis, dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and Western blot analysis. Moreover, miR-216a overexpression inhibited the Wnt/β-catenin signaling pathway. The restoration of LGR5 expression markedly reversed the antitumor effect of miR-216a in glioma cells. Taken together, these findings suggest a tumor suppressor role for miR-216a in gliomas, which inhibits glioma cell proliferation, migration, and invasion by targeting LGR5. Our study suggests that miR-216a may serve as a potential therapeutic target for future glioma treatment.

Key words: Glioma; Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5); Proliferation; Migration; Invasion

1These authors provided equal contribution to this work and are co-first authors.
Address correspondence to Xi Xu, Department of Human Anatomy, Xi’an Medical University, No. 1 Xinwang Road, Weiyang District, Xi’an, Shaanxi 710021, P.R. China. Tel: +86-029-86177556; Fax: +86-029-86177362; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Yingfang Tian, College of Life Sciences, Shaanxi Normal University, No. 620 West Chang’an Avenue, Chang’an District, Xi’an, Shaanxi 710119, P.R. China. Tel: +86-029-85310266; Fax: +86-029-85310266; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1329-1340, 2017
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DOI: https://doi.org/10.3727/096504017X14876227286564
E-ISSN 1555-3906
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TRAF4 Regulates Migration, Invasion, and Epithelial–Mesenchymal Transition via PI3K/AKT Signaling in Hepatocellular Carcinoma

Kairui Liu,* Xiaolin Wu,* Xian Zang,† Zejian Huang,* Zeyu Lin,‡ Wenliang Tan,* Xiang Wu,* Wenrou Hu,* Baoqi Li,* and Lei Zhang*

*Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, P.R. China
†Physical Examination Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, P.R. China
‡Department of Hepatobiliary Surgery, The Six Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, P.R. China

Overexpression of the tumor necrosis factor receptor-associated factor 4 (TRAF4) has been detected in many cancer types and is considered to foster tumor progression. However, the role of TRAF4 in hepatocellular carcinoma (HCC) remains elusive. In this study, we found that TRAF4 was highly expressed in HCC cell lines and HCC tissues compared with normal liver cell lines and adjacent noncancerous tissues. TRAF4 overexpression in HCC tissues was correlated with tumor quantity and vascular invasion. In vitro studies showed that TRAF4 was associated with HCC cell migration and invasion. An in vivo study verified that TRAF4 overexpression facilitated metastasis in nude mice. In addition, overexpressed TRAF4 promoted the phosphorylation of Akt and induced Slug overexpression, leading to downregulated E-cadherin and upregulated vimentin, while silencing TRAF4 moderated the phosphorylation of Akt and repressed the expression of Slug, which resulted in upregulated E-cadherin and downregulated vimentin. These effects were inversed after pretreatment of the PI3K/Akt inhibitor LY294002 or overexpression of constitutively active Akt1. Our study demonstrated that TRAF4 was involved in promoting HCC cell migration and invasion. The process was induced by the EMT through activation of the PI3K/Akt signaling pathway.

Key words: Tumor necrosis factor receptor-associated factor 4 (TRAF4); Hepatocellular carcinoma (HCC); Epithelial–mesenchymal transition (EMT); PI3K/Akt signaling pathway

Address correspondence to Lei Zhang, M.D., Ph.D., Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang West Road, Guangzhou, 510120 Guangdong Province, P.R. China. Tel: 0086-13602730646; Fax: (86)-20-34070926;

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Oncology Research, Vol. 25, pp. 1341-1348, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X14867268787969
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

miR-181a Inhibits Cervical Cancer Development via Downregulating GRP78

Chengyan Luo and Jiangnan Qiu

Department of Gynecology, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, Nanjing, P.R. China

Cervical cancer is among the most common cancers inflicting women worldwide. Understanding the pathological mechanisms of cervical cancer development is critical for identifying novel targets for cervical cancer treatment. MicroRNAs (miRs) have various roles in regulating cancer development. In this study, we investigated the potential role of miR-181a and its target in regulating cervical cancer development and chemotherapy resistance. The expression of miR-181a was evaluated and modulated in several human cervical cancer cell lines. The role of miR-181a in regulating cervical cancer growth and chemotherapy sensitivity was investigated in cell culture models and mouse tumor xenograft models. The target of miR-181a and its function were identified in cervical cancer models. We found a distinct expression profile for miR-181a in cervical cancer cell lines. Low expression of miR-181a was closely related to cervical cancer growth and oxaliplatin resistance. HSPA5/GRP78 was identified as a target of miR-181a in cervical cancer cells. Upregulation of GRP78 led to a high cell proliferation rate and oxaliplatin resistance in cervical cancer models. In a retrospective cervical cancer cohort, high GRP78 expression was correlated with poor survival. miR-181a suppressed cervical cancer development via downregulating GRP78. High expression of GRP78 is a tumor-promoting factor in cervical cancer and is thus a potential target for novel treatment.

Key words: Cervical cancer; MicroRNA-181a; Oxaliplatin; Glucose-regulated protein 78 (GRP78); Tumor development

Address correspondence to Chengyan Luo, Department of Gynecology, Jiangsu Province Hospital, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1349-1355, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X14874337324615
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Knockdown of Angiopoietin-Like Protein 2 Inhibits Proliferation and Invasion in Glioma Cells via Suppressing the ERK/MAPK Signaling Pathway

Li-Kun Yang,*1 Jie Zhu,*1 Yu-Hua Chen,†1 Dong-Liang Wang,‡ Hua Li,§ Liang-Jun Zhang,§ Jing-Ru Zhou,‡ and Wei Liu†

*Department of Neurosurgery, 101th Hospital of PLA, Rescue Center of Craniocerebral Injuries of PLA, Wuxi, P.R. China
†Basic Medical Sciences Research Center, Shaanxi Fourth People’s Hospital, Xi’an, P.R. China
‡Department of Neurosurgery, Peking University People’s Hospital, Beijing, P.R. China
§Department of Neurosurgery, Shaanxi Fourth People’s Hospital, Xi’an, P.R. China

Angiopoietin-like protein 2 (ANGPTL2), a member of the glycoprotein family, is mainly secreted by adipose tissues under normal conditions. Recently, ANGPTL2 has been found to be upregulated in some types of cancers and is considered to be a tumor promoter. However, the functional significance of ANGPTL2 in glioma has not yet been elucidated. In this study, we investigated the specific role of ANGPTL2 in glioma. The results showed that ANGPTL2 was highly expressed in glioma tissues and cell lines. Knockdown of ANGPTL2 reduced the proliferative and invasive abilities of glioma cells. Moreover, the tumorigenesis assay showed that ANGPTL2 knockdown inhibited glioma tumor growth in vivo. We also found that ANGPTL2 knockdown decreased the protein levels of p-ERK1/2 in glioma cells and thus blocked the activity of the ERK/MAPK signaling pathway. Taken together, our study provided the first evidence that ANGPTL2 played an oncogenic role in glioma development and might be considered as a new therapeutic target for glioma treatment.

Key words: Angiopoietin-like protein 2 (ANGPTL2); Proliferation; Invasion; Glioma

1These authors provided equal contribution to this work.
Address correspondence to Jing-Ru Zhou, Department of Neurosurgery, Peking University People’s Hospital, No. 11 Xizhimen South Street, Beijing 100044, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Wei Liu, Basic Medical Sciences Research Center, Shaanxi Fourth People’s Hospital, No. 512 Xianning East Road, Xi’an 710043, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1357-1362, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X14889842609577
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Phase II Trial of Intensity-Modulated Radiotherapy Concurrent With Chemotherapy for Postoperative Node-Positive Esophageal Squamous Cell Carcinoma

Hua Tao, Yiqin Zhou, Chengyun Yao, Dayong Gu, Wei Chen, and Jincheng Lu

Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliate Cancer Hospital, Nanjing, Jiangsu, P.R. China

The aim of this study was to evaluate the efficacy and toxicity of intensity-modulated radiotherapy concurrent with weekly docetaxel in patients with node-positive esophageal squamous cell carcinoma after radical surgery. Between January 2011 and December 2013, a total of 46 eligible patients were enrolled. All patients received intensity-modulated radiotherapy concurrent with weekly docetaxel (20 mg/m2). Patients were treated 5 days per week at 2.0 Gy/day. The total dose of external radiotherapy given was 50 Gy in 25 fractions. The primary endpoints included treatment completion and safety. The secondary endpoint was to assess whether the approach would achieve a 1-year survival rate of 80% or higher. The median duration of follow-up was 18 months (range: 2–41 months). The 1-year overall survival and progression-free survival rate were 91.2% and 80.4%, respectively. The major acute toxicities were esophagitis and neutropenia. While most cases were grade 1 or 2, grade 3 neutropenia and esophagitis were observed in seven (15.2%) and five patients (10.9%), respectively. The toxicities were controllable and transitory. There were no unexpected cases of serious adverse events or treatment-related deaths. Our study confirms that intensity-modulated radiotherapy with concurrent weekly docetaxel is an effective and safe treatment in postoperative node-positive patients with esophageal squamous cell carcinoma. The identified treatment regimen is of interest for a phase III trial.

Key words: Esophageal cancer; Radical surgery; Intensity-modulated radiotherapy; Chemotherapy; Chemoradiotherapy (CRT)

Address correspondence to Jincheng Lu, Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliate Cancer Hospital, 42 Baiziting Street, Nanjing, Jiangsu 210009, P.R. China. Tel: +86-25-83284653; Fax: +86-25-83641062; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1363-1371, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X14878536973557
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Function of miR-152 as a Tumor Suppressor in Human Breast Cancer by Targeting PIK3CA

Shuke Ge,* Dan Wang,† Qinglong Kong,‡ Wei Gao,* and Jiayi Sun*

*Second Department of Breast and Thyroid Surgery, Dalian Municipal Central Hospital Affiliated to Dalian Medical University, Dalian, P.R. China
†Department of General Surgery, The Third People’s Hospital of Dalian, Dalian, P.R. China
‡Department of Thoracic Surgery, Dalian Municipal Central Hospital Affiliated to Dalian Medical University, Dalian, P.R. China

miR-152, as a tumor suppressor, has been reported to be downregulated in a number of cancer cell lines and tumor tissues, including breast cancer. This study aimed to investigate the role of miR-152 in human breast cancer and its underlying mechanisms. Human breast cancer cell line HCC1806 was transfected with hsa-miR-152-3p mimic, inhibitor, or scrambled negative controls. The efficiency of miR-152-3p transfection was evaluated by quantitative real-time PCR, and the effects on cell viability and apoptosis as well as on the PI3K/AKT signaling pathway were investigated by MTT assay, flow cytometry, and Western blot analysis, respectively. The binding effect of miR-152-3p on PIK3CA 3′-UTR was also investigated. The results suggested that miR-152-3p mimic transfection inhibited cell viability while inducing apoptosis of HCC1806 cells. Furthermore, miR-152-3p negatively regulated PIK3CA expression via binding to the 3′-UTR of PIK3CA and decreased the phosphorylation levels of AKT (Ser473) and RPS6 (Ser235/236) in HCC1806 cells. miR-152-3p inhibitor transfection showed the opposite effects. In conclusion, miR-152-3p might serve as a tumor suppressor in human breast cancer cells via negatively regulating PIK3CA expression to inhibit the activation of AKT and RPS6, leading to suppression of HCC1806 cell proliferation.

Key words: miR-152; Tumor suppressor; Breast cancer; PIK3CA; Proliferation; Apoptosis

Address correspondence to Shuke Ge, Second Department of Breast and Thyroid Surgery, Dalian Municipal Central Hospital Affiliated to Dalian Medical University, No. 826 Xi’nan Road, Shahekou District, Dalian 116033, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1373-1382, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X14878509668646
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Highly Expressed Antisense Noncoding RNA in the INK4 Locus Promotes Growth and Invasion of Renal Clear Carcinoma Cells via the β-Catenin Pathway

Qingchun Li,* Yuan Tian,† Guangrui Hu,† Yun Liang,† Wei Bai,† and Hongjun Li†

*Department of Gastrointestinal Colorectal and Anal Surgery, China–Japan Union Hospital of Jilin University, Changchun, P.R. China
†Center of Physical Examination, China–Japan Union Hospital of Jilin University, Changchun, P.R. China

Long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) is involved in several human cancers. However, the role of ANRIL in renal cell carcinoma (RCC) remains unclear. This study aimed to explore whether, and how, ANRIL affects the progression of RCC. First, the expression of ANRIL in clinical tumor tissues and four kinds of RCC cell lines was evaluated. After transfection, cell viability, colony number, apoptosis, migration, and invasion were assessed. The expression of proteins related to apoptosis, epithelial-to-mesenchymal transition (EMT), and the β-catenin signaling pathway was then assessed. In addition, the effect of IWR-endo (β-catenin inhibitor) on cell viability, migration, and invasion, as well as b-catenin expression, was also evaluated. The results showed that ANRIL was highly expressed in RCC tissues and RCC cell lines. ANRIL significantly promoted cell proliferation, migration, invasion, and EMT but inhibited cell apoptosis. Additionally, the expression levels of β-catenin, Ki-67, glycogen synthase kinase 3β (GSK-3β), phosphorylated GSK-3β, T-cell transcription factor 4 (TCF-4), and leukemia enhancer factor 1 (LEF-1) were all markedly upregulated by ANRIL. The effect of ARNIL silencing was opposite to that of ANRIL overexpression. The effect of ARNIL on proliferation, migration, and invasion of RCC cells was found to be reversed by IWRendo. In conclusion, ANRIL, which is highly expressed in RCC, acted as a carcinogen in RCC cells through the activation of the β-catenin pathway.

Key words: Long noncoding RNA ANRIL; Renal clear cell carcinoma; Invasion; β-Catenin signaling pathway

Address correspondence to Hongjun Li, Center of Physical Examination, China–Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin Province, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1383-1390, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X14879366402279
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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miR-101-3p Suppresses HOX Transcript Antisense RNA (HOTAIR)-Induced Proliferation and Invasion Through Directly Targeting SRF in Gastric Carcinoma Cells

Xiaoyu Wu,*1 Jin Zhou,†1 Zhenfeng Wu,* Che Chen,* Jiayun Liu,* Guannan Wu,* Jing Zhai,* Fukun Liu,* and Gang Li‡

*Department of Surgical Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, P.R. China
†Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China
‡Department of General Surgery, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, P.R. China

miR-101-3p has been identified as a tumor suppressor in several cancers, but its exact role in gastric adenocarcinoma is still largely unknown. In this study, we found that, compared with the RGM-1 human normal gastric epithelial cells, miR-101-3p was significantly downregulated in all six human gastric adenocarcinoma cell lines, including BGC-823, MNK-45, MGC-803, SGC-7901, AGS, and HGC-27. Overexpression of miR-101-3p suppressed both the proliferation and invasion of AGS gastric adenocarcinoma cells, and knockdown of miR-101-3p displayed the opposite effect. In addition, miR-101-3p could directly target and suppress the expression of the serum response factor (SRF) gene, which is a transcription factor of HOTAIR, a well-characterized tumor promoter lncRNA. miR-101-3p negatively regulated SRF-mediated transcription of HOTAIR. Moreover, silencing of either SRF or HOTAIR could counteract the promotion of gastric adenocarcinoma cell proliferation and invasion by miR-101-3p inhibition. Our findings indicate that miR-101-3p suppresses HOTAIR-induced proliferation and invasion through directly targeting SRF in gastric carcinoma cells.

Key words: miR-101-3p; Gastric carcinoma; Proliferation and invasion; Serum response factor (SRF); HOX transcript antisense RNA (HOTAIR)

1These authors provided equal contribution to this work.
Address correspondence to Gang Li, Department of General Surgery, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, 42 Baiziting, Nanjing 210009, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1391-1398, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X14881559833562
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Long Noncoding RNA PVT1 Facilitates Cervical Cancer Progression via Negative Regulating of miR-424

Ya-Li Gao,*1 Zi-Shen Zhao,†1 Ming-Yun Zhang,* Li-Jie Han,* Yu-Jin Dong,‡ and Bo Xu‡

*Department of Radiotherapy, Cangzhou Central Hospital, Cangzhou, Hebei, P.R. China
†Department of Dermatology, Cangzhou People’s Hospital, Cangzhou, Hebei, P.R. China
‡Department of Radiotherapy, Zibo Central Hospital, Zibo, Shandong, P.R. China

Emerging evidence suggests that the long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) gene is involved in the pathogenesis of cervical cancer. However, the potential mechanism is rarely reported. Our study found that PVT1 was upregulated in cervical cancer tissue and cell lines. After transfecting PVT1 siRNA, the proliferation, migration, and invasion of cervical cancer cells were markedly decreased. miRNA expression profiles demonstrate that miR-424 was markedly downregulated in cervical cancer tissue. Bioinformatics analysis revealed that miR-424 was potentially targeted by PVT1, which was confirmed by dual-luciferase reporter assay. Pearson’s correlation analysis showed that PVT1 expression was negatively related to miR-424 expression in glioma cancer tissues. Finally, lowered expression of miR-424 could recover the tumor-suppressive effects of PVT1 knockdown in cervical cancer cell lines. Our results reveal a tumor-promoting role for PVT1, acting as a competing endogenous RNA (ceRNA) or a molecular sponge in negatively modulating miR-424, which might provide a novel therapeutic target for cervical cancer.

Key words: Plasmacytoma variant translocation 1 (PVT1); miR-424; Cervical cancer; Competing endogenous RNA (ceRNA)

1These authors provided equal contribution to this work.
Address correspondence to Yu-Jin Dong, M.D., Department of Radiotherapy, Zibo Central Hospital, No. 54 Gongqingtuan Road, Zhangdian District, Zibo, Shandong 255020, P.R. China. Tel: +86-0533-2360101; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Bo Xu, M.D., Department of Radiotherapy, Zibo Central Hospital, No. 54 Gongqingtuan Road, Zhangdian District, Zibo, Shandong 255020, P.R. China. Tel: +86-0533-2360101; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1399-1407, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14823648620870
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Gastrin Enhances Autophagy and Promotes Gastric Carcinoma Proliferation via Inducing AMPKα

Zhuang Kun,*† Guo Hanqing,* Tang Hailing,* Yan Yuan,* Zhang Jun,† Zhang Lingxia,* Han Kun,* and Zhang Xin*

*Division of Gastroenterology, Xi’an Central Hospital, Xi’an, P.R. China
†Division of Gastroenterology, The Second Affiliated Hospital Xi’an Jiaotong University, Xi’an, P.R. China

Gastric cancer (GC) is one of the most frequent epithelial malignancies worldwide. The gastrointestinal (GI) peptide gastrin is an important regulator of the secretion and release of gastric acid from stomach parietal cells, and it also plays a vital role in the development and progression of GC. The aim of the current study was to investigate the role and underlying mechanism of gastrin and autophagy in regulating GC tumorigenesis. Gastrin-17 amide (G-17) was applied in the GC cell lines SGC7901 and MGC-803. The results showed that G-17 maintained the high viability of SGC7901 and MGC-803. The expression of autophagy marker proteins LC3II and Beclin1 was significantly increased, while the autophagy substrate p62 was obviously decreased in the gastrin group compared with the control group. Moreover, G-17 strengthened the expressions of AMPKα, Ras, Raf, MEK, and ERK1/2. Additionally, administration of AMPKα siRNA counteracted the effect of gastrin in SGC7901 cells. Finally, in an in vivo study of the tumor growth and survival rate of rats, the levels of AMPKα/Ras/Raf/MEK/ERK were significantly increased in the gastrin group and decreased following AMPKα shRNA injection. In conclusion, these findings indicate that gastrin plays a tumorigenic role by promoting autophagy in GC and may provide a novel therapeutic target for GC treatment.

Key words: Gastric cancer (GC); Gastrin; Autophagy; AMP-activated protein kinase (AMPKα)

Address correspondence to Zhuang Kun, Division of Gastroenterology, Xi’an Central Hospital, No. 161 Xi Wu Road, Xi’an 710003, P.R. China. Tel: (86)29-87678009; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1409-1419, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X14882829077237
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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MicroRNA-107 Promotes Proliferation, Migration, and Invasion of Osteosarcoma Cells by Targeting Tropomyosin 1

Rui Jiang,* Chao Zhang,† Guangyao Liu,* Rui Gu,* and Han Wu*

*Department of Orthopedics, China–Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China
†Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, P.R. China

Osteosarcoma is the most common primary bone malignancy manifested predominantly in children and young adults. Studies indicate that miR-107 is involved in the pathogenesis of osteosarcoma and that tropomyosin 1 (TPM1) acts as a tumor suppressor in many types of cancer. In this study, we analyzed the effect of miR-107 on human osteosarcoma cells and investigated the mechanism in which TPM1 is involved. miR-107 expression in human osteosarcoma tissues and cells was analyzed in quantitative real-time PCR (qRT-PCR). Human osteosarcoma (U2OS) cells were transfected with miR-107 mimic, inhibitor, or scramble controls to evaluate the effect of miR-107 on cellular migration and invasion, cell viability, and apoptosis. Cells were cotransfected with the miR-107 mimic and TPM1 3′-UTR wild-type (wt) recombinant vector or mutant type (mt) as a negative control. The binding effect of miR-107 on TPM1 3′-UTR was determined by dual-luciferase reporter assay. The expression of TPM1, apoptosis-related proteins, and signaling molecules was determined by qRT-PCR and Western blotting. The results showed that miR-107 expression was upregulated in osteosarcoma tissues and cell lines. miR-107 overexpression promoted U2OS cell viability, migration, and invasion whereas it inhibited apoptosis. miR-107 inhibitor transfection ameliorated or abolished these effects after miR-107 binding to TPM1 3′-UTR-wt regulated TPM1 expression. miR-107 in U2OS cells activated MEK/ERK and NF-κB signaling pathways via TPM1. In conclusion, miR-107 overexpression promoted U2OS cell viability, migration, and invasion via downregulation of TPM1 and might be through activating the MEK/ERK and NF-κB signaling pathways.

Key words: Osteosarcoma; miR-107; Tropomyosin 1 (TPM1); MEK/ERK; NF-κB

Address correspondence to Professor Han Wu, Department of Orthopedics, China–Japan Union Hospital of Jilin University, No. 126, Xiantai Street, Changchun, Jilin Province 130033, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it