Oncology Research 25(1) Abstracts

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Oncology Research, Vol. 25, pp. 1-10, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14685034103798
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

MicroRNA-200a Suppresses Cell Invasion and Migration by Directly Targeting GAB1 in Hepatocellular Carcinoma

Jianlin Wang,*1 Wenjie Song,*1 Weiwei Shen,†1 Xisheng Yang,* Wei Sun,* Sshibin Qu,* Runze Shang,* Ben Ma,* Meng Pu,* Kaishan Tao,* Kefeng Dou,* and Haimin Li*

*Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, P.R. China
†Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, P.R. China

MicroRNA-200a (miR-200a) is frequently downregulated in most cancer types and plays an important role in carcinogenesis and cancer progression. In this study, we determined that miR-200a was downregulated in hepatocellular carcinoma (HCC) tissues and cell lines, consistent with the results of our previous study. Because a previous study suggested that downregulation of miR-200a is correlated with HCC metastasis, we aimed to elucidate the mechanism underlying the role of miR-200a in metastasis in HCC. Here we observed that overexpression of miR-200a resulted in suppression of HCC metastatic ability, including HCC cell migration, invasion, and metastasis, in vitro and in vivo. Furthermore, bioinformatics and luciferase reporter assays indicated that GAB1 is a direct target of miR-200a. Inhibition of GAB1 resulted in substantially decreased cell invasion and migration similar to that observed with overexpression of miR-200a in HCC cell lines, whereas restoration of GAB1 partially rescued the inhibitory effects of miR-200a. Taken together, these data provide novel information for comprehending the tumor-suppressive role of miR-200a in HCC pathogenesis through inhibition of GAB1 translation.

Key words: miR-200a; Hepatocellular carcinoma (HCC); Grb2-associated binding protein 1 (GAB1); Invasion and migration; Metastasis

1These authors provided equal contribution to this work.
Address correspondence to Haimin Li, Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Changle Street, Xi’an, Shaanxi 710032, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Kefeng Dou, Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Changle Street, Xi’an, Shaanxi 710032, 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. 11-18, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14685034103833
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Overexpression of Aristaless-Like Homeobox-4 Inhibits Proliferation, Invasion, and EMT in Hepatocellular Carcinoma Cells

Yao Shi,* Xiaoke Sun,† and Xiafen He‡

*Control of Nosocomial Infections, Hong-hui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, P.R. China
†Department of Surgery, Hong-hui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, P.R. China
‡Basic Medical College of Xi’an Jiaotong University, Xi’an, P.R. China

Aristaless-like homeobox-4 (ALX4), a member of the Aristaless-like homeobox family, has been found to be involved in tumor cell proliferation, migration, and invasion. However, the role of ALX4 in hepatocellular carcinoma (HCC) remains largely unclear. Therefore, in this study we investigated the effects of ALX4 on HCC. The study results indicated that the expression of ALX4 was downregulated in HCC tissues and cell lines. Furthermore, we demonstrated that overexpression of ALX4 inhibited the proliferation, invasion, and epithelial–mesenchymal transition (EMT) in HCC cells. We also found that ALX4 had an inhibitory effect on the sonic hedgehog (Shh) signaling pathway. Taken together, the results suggest that ALX4 may be a promising target for HCC treatment.

Key words: Aristaless-like homeobox-4 (ALX4); Proliferation; Invasion; Epithelial–mesenchymal transition (EMT); Hepatocellular carcinoma (HCC)

Address correspondence to Xiaoke Sun, Department of Surgery, Hong-hui Hospital, Xi’an Jiaotong University College of Medicine, No. 555 Youyi East Road, Xi’an 710054, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Xiafen He, Basic Medical College of Xi’an Jiaotong University, No. 76 Yanta West Road, Xi’an 710061, 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. 19-27, 2017
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DOI: https://doi.org/10.3727/096504016X14685034103914
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Knockdown of Rap2B Inhibits the Proliferation and Invasion in Hepatocellular Carcinoma Cells

Li Zhang,* Hong-bin Duan,† and Yun-sheng Yang*

*Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, P.R. China
†Emergency Department, Shanxi Provincial People’s Hospital, Taiyuan, P.R. China

Rap2B, a member of the Ras family of small GTP-binding proteins, was found to be highly expressed in various human tumors and plays an important role in the development of tumors. However, the function of Rap2B in hepatocellular carcinoma (HCC) remains unclear. Therefore, in this study, we investigated the biological functions of Rap2B in HCC and the potential underlying mechanisms. Our results indicated that Rap2B was highly expressed in HCC tissues and cell lines. Rap2B silencing obviously inhibited the proliferation, migration, and invasion of HCC cells, as well as attenuated xenografted tumor growth in vivo. Furthermore, Rap2B silencing greatly reduced the expression levels of phosphorylated focal adhesion kinase (p-FAK), matrix metalloproteinase-2 (MMP-2), and MMP-9 in HCC cells. In conclusion, our data suggest that Rap2B silencing inhibits the proliferation and invasion in HCC cells. Thus, Rap2B may have potential as a treatment for HCC.

Key words: Rap2B; Hepatocellular carcinoma (HCC); Proliferation; Invasion; FAK pathway

Address correspondence to Yun-sheng Yang, Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, 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. 29-34, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14719078133168
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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MicroRNA-377 Downregulates Bcl-xL and Increases Apoptosis in Hepatocellular Carcinoma Cells

Hongyan Ge,* Di Zou,† Yingshu Wang,* Hao Jiang,* and Liping Wang‡

*Department of Gastroenterology, Affiliated Hospital of Inner Mongolia University for the Nationalities/Clinical Medicine College of Inner Mongolia University for the Nationalities, Tongliao, P.R. China
†Department of Nephrology, The First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, P.R. China
‡Department of Gastroenterology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, P.R. China

Aberrantly expressed microRNAs (miRNAs/miRs) and their role in cancer development have recently gained more attention. However, the potential role of miRNAs in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we demonstrated that miR-377 was markedly downregulated in HCC cell lines and primary human HCC tissues. The decreased expression of miR-377 contributes to the upregulation of Bcl-xL expression by targeting its 3ʹ-untranslated region (3ʹ-UTR). Functionally, knockdown of miR-377 noticeably increased HCC cell growth and colony formation and inhibited apoptosis. In contrast, overexpression of miR-377 suppressed cell proliferation and increased apoptosis. This study provides new insights for the use of miR-377 as a potential molecular target in HCC therapy.

Key words: miR-377; Hepatocellular carcinoma (HCC); Apoptosis; Bcl-xL

Address correspondence to Liping Wang, Department of Gastroenterology, The Affiliated Hospital of Inner Mongolia Medical University, No. 1 Channel North Street, Hui District, Hohhot 028000, 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. 35-42, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14719078133249
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

The Biological Effects of Dickkopf1 on Small Cell Lung Cancer Cells and Bone Metastasis

Hailin Pang,1 Ningqiang Ma,1 Mi Jiao, Weiwei Shen, Bo Xin, Tongfei Wang, Feng Zhang, Lili Liu, and Helong Zhang

Department of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi’an, Shaanxi, P.R. China

The bone is among the most common sites of metastasis in patients with lung cancer. Over 30%–40% of lung cancers can develop bone metastasis, and no effective therapeutic methods exist in clinic cases. Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferentially metastasizes to the skeleton. However, the role of DKK1 in osteotropism of small cell lung cancer (SCLC) remains to be elucidated. This study aimed to define the role of DKK1 in SCLC bone metastasis and investigate

the underlying mechanisms. Our results demonstrated that the expression level of DKK1 was dramatically higher in bone metastatic SCLC cells (SBC-5 cell line) compared with that in cells without bone metastatic ability (SBC-3 cell line). Therefore, we hypothesized that DKK1 was involved in the bone metastasis of SCLC. We then suppressed the DKK1 expression in SBC-5 cells by RNAi and found that downregulation of DKK1 can inhibit cell proliferation, colony formation, cell migration, and invasion, but increase the apoptosis rate. Downregulation of DKK1 did not affect the cell cycle progression of SBC-5 cells in vitro. In vivo, downregulated DKK1 in SBC-5 cells resulted in attenuated bone metastasis. These results indicated that DKK1 may be an important regulator in bone metastases of SCLC, and targeting DKK1 may be an effective method to prevent and treat skeleton metastases in SCLC cases.

Key words: Dickkopf1 (DKK1); Bone metastasis; Small cell lung cancer (SCLC)

1These authors provided equal contribution to this work.
Address correspondence to Professor Lili Liu, Department of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi’an, Shaanxi 710038, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Professor Helong Zhang, Department of Oncology, Tangdu Hospital, the Fourth Military Medical University, Xi’an, Shaanxi 710038, 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. 43-53, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14719078133285
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Inhibition of Beclin-1-Mediated Autophagy by MicroRNA-17-5p Enhanced the Radiosensitivity of Glioma Cells

Weichen Hou,* Lei Song,† Yang Zhao,* Qun Liu,* and Shuyan Zhang‡

*Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, P.R. China
†Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin Province, P.R. China
‡Department of Neurotrauma, The First Hospital of Jilin University, Changchun, Jilin Province, P.R. China

The role of miRNAs in the radiosensitivity of glioma cells and the underlying mechanism is still far from clear. In the present study, we detected six downregulated and seven upregulated miRNAs in the serum after radiotherapy compared with paired serum samples before radiotherapy via miRNA panel PCR. Among these, miR-17-5p was highly reduced (fold change = −4.21). Further, we validated the levels of miR-17-5p in all serum samples with qRT-PCR. In addition, statistical analysis suggested that a reduced miR-17-5P level was positively associated with advanced clinical stage of glioma, incidence of relapse, and tumor differentiation. Moreover, we provided evidence that irradiation markedly activated autophagy and decreased miR-17-5p in the glioma cell line. Further, we demonstrated that irradiation-induced autophagy activation was mediated by beclin-1, and downregulation of beclin-1 via siRNA significantly abolished the irradiation-activated autophagy. Interestingly, we demonstrated that miR-17-5p could directly target beclin-1 via luciferase gene reporter assay. Exotic expression of miRNA-17-5p decreased autophagy activity in vitro. In nude mice, miRNA-17-5p upregulation sensitized the xenograft tumor to irradiation and suppressed irradiation-induced autophagy. Finally, pharmacal inhibition of autophagy markedly enhanced the cytotoxicity of irradiation in RR-U87 cells.

Key words: Glioma; MicroRNA-17-5p; Beclin-1; Autophagy; Radiosensitivity

Address correspondence to Qun Liu, Department of Neurology, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun, Jilin Province 130000, P.R. China. Fax: 0431-85634303; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or ShuyanZhang, Department of Neurotrauma, The First Hospital of Jilin University, No. 71 Xinmin Street, Changchun, Jilin Province 130000, P.R. China. Fax: 0431-85676227; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 55-63, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14719078133320
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Tumor Necrosis Factor (TNF)-α-Induced Protein 8-like-2 (TIPE2) Inhibits Proliferation and Tumorigenesis in Breast Cancer Cells

Ke Wang, Yu Ren, Yang Liu, Jian Zhang, and Jian-jun He

Department of Breast Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China

Tumor necrosis factor- α (TNF- α)-induced protein 8-like-2 (TNFAIP8L2 or TIPE2), a member of the tumor necrosis TNFAIP8 family, was found to be involved in the development and progression of several tumors. However, to date, the role of TIPE2 in breast cancer is still unclear. Thus, the aim of this study is to explore the role of TIPE2 in breast cancer. Our results indicated that TIPE2 expression was significantly decreased in human breast cancer tissue and cell lines. Overexpression of TIPE2 inhibited the proliferation in vitro and tumor xenograft growth in vivo. TIPE2 also inhibited the migration/invasion of breast cancer cells through preventing the epithelial-to-mesenchymal transition (EMT) phenotype. Mechanically, TIPE2 inhibited the expression of β-catenin, cyclin D1, and c-Myc in breast cancer cells. In conclusion, our findings show that TIPE2 may play an important role in breast cancer cell proliferation, invasion, and tumorigenesis in vivo. Therefore, TIPE2 may be a potential molecular target for the treatment of breast cancer.

Key words: Tumor necrosis factor (TNF)- α -induced protein 8-like-2 (TIPE2); Breast cancer; Invasion; Wnt/β-catenin pathway

Address correspondence to Jian-jun He, Department of Breast Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an 710061, P.R. China. Tel: +86-029-85324605; Fax: +86-029-85324605; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 65-73, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14719078133366
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

MicroRNA-142-5p Overexpression Inhibits Cell Growth and Induces Apoptosis by Regulating FOXO in Hepatocellular Carcinoma Cells

Kexin Lou,*1 Ning Chen,†1 Zhihong Li,* Bei Zhang,† Xiuli Wang,‡ Ye Chen,* Haining Xu,* Dongwei Wang,* and Hao Wang*

*Department of Ultrasound, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China
†Department of Gynecology and Obstetrics, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China
‡Central Laboratory, Xuzhou Central Hospital, Xuzhou, Jiangsu, P.R. China

Abnormal expression of microRNA (miR)-142-5p has been reported in hepatocellular carcinoma (HCC). However, little information is available regarding the functional role of miR-142-5p in HCC. We aimed to explore the effects of miR-142-5p aberrant expression on HCC cell growth and cell apoptosis, as well as the underlying mechanism. Human HCC cell lines HepG2 and SMMC-7721 cells were transfected with miR- 142-5p mimic, inhibitor, or a corresponding negative control. Cell viability, cell cycle distribution, and cell apoptosis were then analyzed. In addition, protein expression of Forkhead box, class O (FOXO) 1 and 3, a Bcl-2-interacting mediator of cell death (Bim), procaspase 3, and activated caspase 3 was measured. After transfection with miR-142-5p inhibitor, FOXO1 and FOXO3 were overexpressed, and then the cell viability and cell apoptosis were determined again. The relative cell viability in both HepG2 and SMMC-7721 cells was significantly reduced by miR-142-5p overexpression (p < 0.05). miR-142-5p overexpression displayed a significant blockage at the G1/S transition and significantly increased the percentages of G0/G1 phase. Moreover, the results showed that miR-142-5p overexpression significantly induced cell apoptosis and statistically elevated the protein expression levels of FOXO1, FOXO3, Bim, procaspase 3, and activated caspase 3. However, the cells transfected with miR-142-5p inhibitor showed contrary results. Additionally, the effects of miR-142-5p inhibitor on cell viability and apoptosis were reversed by overexpression of FOXO. In conclusion, our results suggest that miR-142-5p overexpression shows an important protective role in HCC by inhibiting cell growth and inducing apoptosis. These effects might be by regulating FOXO expression in HCC cells.

Key words: MicroRNA-142-5p; Hepatocellular carcinoma (HCC); Cell growth; Cell apoptosis; Forkhead box, class O (FOXO)

1These authors provided equal contribution to this work.
Address correspondence to Zhihong Li, Department of Ultrasound, Xuzhou Central Hospital, No. 199, Jiefang Road, Xuzhou, Jiangsu 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. 75-81, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14719078133401
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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miR-214-5p Targets ROCK1 and Suppresses Proliferation and Invasion of Human Osteosarcoma Cells

Minglei Zhang,* Dapeng Wang,† Tongtong Zhu,* and Ruofeng Yin*

*Department of Orthopaedics, China–Japan Union Hospital, Jilin University, Changchun, P.R. China
†Department of Orthopaedics, Si-ping Central Hospital, Siping, P.R. China

MicroRNAs (miRNAs) are small conserved RNAs regulating specific target genes in posttranscriptional levels. They have been involved in multiple processes of tumor progression, including cell proliferation. miR-214-5p (also miR-214*) is a newly identified miRNA, and its functions are largely unknown. In this study, we explore the role of miR-214-5p in the proliferation and invasion of human osteosarcoma (OS) cells. The results showed that miR-214-5p was sharply reduced in OS tissues and cell lines, compared with normal tissues and cell lines. In addition, the miR-214-5p mimic greatly increased the miR-214-5p level and significantly decreased the proliferation and invasion of HOS and G293 OS cells. In contrast, the miR-214-5p inhibitor had a completely opposite effect on the miR-214-5p level, cell proliferation, and cell invasion. Moreover, bioinformatics and luciferase reporter gene assays confirmed that miR-1908 targeted the mRNA 3ʹ-UTR region of ROCK1, a characterized tumor promoter in OS. In conclusion, miR-214-5p was identified as a new tumor suppressor, which directly targeted ROCK1 and suppressed proliferation of human OS cells.

Key words: miR-214-5p; Cell proliferation; Human osteosarcoma (OS); ROCK1

Address correspondence to Ruofeng Yin, Department of Orthopaedics, China–Japan Union Hospital, Jilin University, No. 126 of Xian-Tai Street, Changchun 130033, P.R. China. Tel: +86-0431-89876909; Fax: +86-0431-89876909; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 83-91, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14719078133447
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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RASSF4 Overexpression Inhibits the Proliferation, Invasion, EMT, and Wnt Signaling Pathway in Osteosarcoma Cells

Minglei Zhang,* Dapeng Wang,† Tongtong Zhu,* and Ruofeng Yin*

*Department of Orthopaedics, China–Japan Union Hospital, Jilin University, Changchun, P.R. China
†Department of Orthopaedics, Si-ping Central Hospital, Siping, P.R. China

RASSF4, a member of the RASSF family, is broadly expressed in normal tissues but often inactivated in human cancers. Despite various studies on RASSF4, its role in osteosarcoma remains unclear. Therefore, in this study, we investigated the effects of RASSF4 expression on osteosarcoma cells and explored the underlying mechanism. The results of our study showed that RASSF4 was lowly expressed in osteosarcoma tissues and cells. RASSF4 overexpression significantly inhibited proliferation, migration, and invasion as well as the EMT process in osteosarcoma cells. Meanwhile, we found that RASSF4 overexpression markedly decreased the protein expression of β-catenin, cyclin D1, and c-Myc in osteosarcoma cells. In conclusion, our findings showed that RASSF4 overexpression inhibits proliferation, invasion, EMT, and Wnt signaling pathway in osteosarcoma cells. Thus, RASSF4 may be considered a novel target for osteosarcoma treatment.

Key words: RASSF4; Osteosarcoma; Proliferation; Invasion; Epithelial–mesenchymal transition (EMT)

Address correspondence to Ruofeng Yin, Department of Orthopaedics, China–Japan Union Hospital, Jilin University, No. 126 of Xian-Tai Street, Changchun 130033, P.R. China. Tel: +86-0431-89876909; Fax: +86-0431-89876909; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 93-97, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14719078133564
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Identification of Sensitivity Predictors of Neoadjuvant Chemotherapy for the Treatment of Adenocarcinoma of Gastroesophageal Junction

Shoumiao Li,*† Baozhong Li,† Jiaxiang Wang,* Da Zhang,* Zhiqiang Liu,† Zhizhong Zhang,† Wei Zhang,† Yunjie Wang,† Dongxiao Bai,† Jianyun Guan,† and Yong Zhang†

*Department of Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
†Department of Surgery, Anyang Tumor Hospital, Anyang, Henan, P.R. China

The identification of reliable predictors of chemotherapy sensitivity and early screening of adenocarcinoma of gastroesophageal junction (AGEJ) patients who are resistant to chemotherapy has become an important area of clinical and translational research. We aimed to investigate the predictive value of seven cancer-associated cellular proteins for neoadjuvant chemotherapy in AGEJ patients. Clinical data of 93 patients who received neoadjuvant chemotherapy for locally advanced AGEJ between June 2010 and December 2014 were reviewed. All patients were administered the combination regimen of S-1 and oxaliplatin (SOX). Expression of P-glycoprotein (P-gp), glutathione S-transferase-p (GST-p), topoisomerase II (topo II), multidrug resistance gene-associated protein (MRP), lung resistance-related protein (LRP), Ki-67, and p53 was determined by immunohistochemistry (IHC) in AGEJ tissues before neoadjuvant chemotherapy. Chemotherapeutic efficacy was evaluated according to RECIST 1.0 standards and histopathological results, and the relationship between the expression of the cellular proteins and chemotherapy efficacy was analyzed. The SOX regimen was associated with an overall response rate of 46.2%. The frequency of expression of the seven cancer-associated factors in the AGEJ tissues was as follows: P-gp, 64.5%; GST-π, 39.8%; topo II, 72.0%; MRP, 33.3%; LRP, 68.8%; Ki-67, 62.4%; and p53, 40.9%. Expression of Ki-67 (p = 0.003) and p53 (p = 0.009) was significantly correlated with chemotherapy sensitivity. Elevated Ki-67 expression and decreased p53 expression predict for SOX insensitivity in AGEJ, and the cellular expression of these respective proteins may provide a useful reference for designing individualized chemotherapy regimens for AGEJ patients in the future.

Key words: Gastroesophageal junction neoplasm; Siewert II type; Neoadjuvant chemotherapy (NACH); Predictive factors; Chemosensitivity

Address correspondence to Jiaxiang Wang, Department of Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. Tel:13938260010; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Baozhong Li, Department of Surgery, Anyang Tumor Hospital, Anyang, Henan 455000, 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. 99-105, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14719078133609
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Silencing of Armadillo Repeat-Containing Protein 8 (ARMc8) Inhibits TGF-β-Induced EMT in Bladder Carcinoma UMUC3 Cells

Xuan Liang,* Qun-Li Men,† Yong-wei Li,‡ He-Cheng Li,§ Tie Chong,§ and Zhao-lun Li§

*Department of Oncology, The First Affiliated Hospital, Xi’an Jiaotong University Medical College, Xi’an, Shaanxi, P.R. China
†Department of Urology, The Central Hospital of Baoji, Baoji, Shaanxi, P.R. China
‡Department of Urology, The Central Hospital of Weinan, Weinan, Shaanxi, P.R. China
§Department of Urology, The Second Affiliated Hospital, Xi’an Jiaotong University Medical College, Xi’an, Shaanxi, P.R. China

Armadillo repeat-containing protein 8 (ARMc8) is a key factor in regulating cell migration, proliferation, tissue maintenance, and tumorigenesis. However, its role in bladder cancer remains unknown. Thus, in this study we sought to investigate the effect of ARMc8 on the epithelial-to-mesenchymal transition (EMT) progress in bladder cancer cells induced by transforming growth factor-β1 (TGF-β1). Our results found that ARMc8 was highly expressed in bladder cancer cell lines. ARMc8 silencing inhibited the TGF-β1-induced migration and invasion and suppressed the EMT progress in bladder cancer cells. Furthermore, ARMc8 silencing inhibited the TGF-b1-induced expression of b-catenin, cyclin D1, and c-myc in bladder cancer cells. In conclusion, the present study demonstrates a novel function for ARMc8, which acts as a mediator for TGF-β1-induced cell migration/invasion through modulation of the Wnt/β-catenin signaling pathway in bladder cancer cells. This study suggests that ARMc8 may be a potential therapeutic target for the development of therapies for bladder cancer.

Key words: Armadillo repeat-containing protein 8 (ARMc8); Bladder cancer; Transforming growth factor-β1 (TGF-β1); Epithelial-to-mesenchymal transition (EMT)

Address correspondence to Zhao-lun Li, Department of Urology, The Second Affiliated Hospital, Xi’an Jiaotong University Medical College, No. 157 of Xiwu Road, Xi’an, Shaanxi 710004, P.R. China. Tel: +86-029-87679533; Fax: +86-029-87679436; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 107-114, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14732772150145
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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miR-940 Upregulation Suppresses Cell Proliferation and Induces Apoptosis by Targeting PKC-δ in Ovarian Cancer OVCAR3 Cells

Fang Wang, Zhihong Wang, Xiaoli Gu, and Jinquan Cui

Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China

Ovarian cancer remains as one of the most threatening malignancies for females in the world. This study investigated the pivotal role of miR-940 in the progression of ovarian cancer and to reveal the possible molecular mechanism of its action. Ovarian cancer OVCAR3 cells were transfected with the miR-940 vector, miR-940 inhibitor, and/or small interfering RNA (siRNA) targeting PKC-δ (si-PKC-δ), respectively. After transfection, cell viability and cell apoptosis were analyzed, as well as cell proliferation and apoptosis-related protein expression. Compared to the control, miR-940 upregulation suppressed cell viability but induced cell apoptosis. miR-940 upregulation increased the expression of p27, Hes1, survivin, and caspase 3, but decreased the expression of PKC-δ. In addition, elevated cell viability induced by the miR-940 inhibitor was significantly decreased by knockdown of PKC-δ, and reduced cell apoptosis induced by the miR-940 inhibitor was increased by knockdown of PKC-δ. Taken together, the results of our study suggest that upregulation of miR-940 may function as a suppressor in the progression of ovarian cancer by inhibiting cell proliferation and inducing apoptosis by targeting PKC-δ. This study may provide a basis for the possible application of miR-940 in illustrating the molecular pathogenic mechanism of ovarian cancer.

Key words: Ovarian cancer; miR-940; Cell proliferation; Cell apoptosis; Protein kinase C-δ (PKC-δ)

Address correspondence to Jinquan Cui, Department of Obstetrics and Gynecology Surgery, The Second Affiliated Hospital of Zhengzhou University, No. 2 Jingba Road, Zhengzhou 450014, 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. 115-122, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14732772150181
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Knockdown of Tripartite Motif-Containing Protein 37 (TRIM37) Inhibits the Proliferation and Tumorigenesis in Colorectal Cancer Cells

Ping Zhao,* Hai-Tao Guan,† Zhi-Jun Dai,† Yu-Guang Ma,† Xiao-Xu Liu,† and Xi-Jing Wang†

*Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, P.R. China
†Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, P.R. China

Tripartite motif-containing protein 37 (TRIM37), a new member of the RING-B-box-coiled-coil (RBCC) subfamily of zinc finger proteins, was found to be involved in the development and progression of several cancers. However, the expression pattern and biological functions of TRIM37 in colorectal cancer (CRC) remain unknown. Therefore, in the present study, we examined the expression pattern of TRIM37 in CRC and investigated the function of TRIM37 in the progression of CRC. Our results showed that TRIM37 expression was upregulated in CRC cell lines. Knockdown of TRIM37 inhibited CRC cell proliferation and tumor growth in vivo. Furthermore, knockdown of TRIM37 inhibited the migration and invasion in CRC cells. Last, knockdown of TRIM37 inhibited the protein level expression of β-catenin, cyclin D1, and c-Myc in CRC cells. In conclusion, these results demonstrate that TRIM37 may play an important role in the proliferation, invasion, and tumorigenesis of CRC cells. Thus, TRIM37 may be a potential therapeutic target for the treatment of CRC.

Key words: Tripartite motif-containing protein 37 (TRIM37); Colorectal cancer (CRC); Proliferation; Invasion

Address correspondence to Hai-Tao Guan, Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, 157 West No. 5 Road, Xi’ an 710004, Shaanxi Province, P.R. China. Tel: +86-029-87678560; Fax: +86-029-87678560; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 123-136, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14732772150226
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Depletion of NFBD1/MDC1 Induces Apoptosis in Nasopharyngeal Carcinoma Cells Through the p53–ROS–Mitochondrial Pathway

Zhihai Wang,* Kui Liao,† Wenqi Zuo,* Xueliang Liu,* Zhili Qiu,* Zhitao Gong,* Chuan Liu,* Quan Zeng,* Yi Qian,* Liang Jiang,* Youquan Bu,‡ Suling Hong,* and Guohua Hu*

*Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China
†Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China
‡Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research, China Center, Chongqing Medical University, Chongqing, P.R. China

NFBD1, a signal amplifier of the p53 pathway, is vital for protecting cells from p53-mediated apoptosis and the early phase of DNA damage response under normal culture conditions. Here we investigated its expression in patients with nasopharyngeal carcinoma (NPC), and we describe the biological functions of the NFBD1 gene. We found that NFBD1 mRNA and protein were more highly expressed in NPC tissues than in nontumorous tissues. To investigate the function of NFBD1, we created NFBD1-depleted NPC cell lines that exhibited decreased cellular proliferation and colony formation, an increase in their rate of apoptosis, and an enhanced sensitivity to chemotherapeutic agents compared with in vitro controls. However, N-acetyl cysteine (NAC) and downregulation of p53 expression could partially reverse the apoptosis caused by the loss of NFBD1. Further analysis showed that loss of NFBD1 resulted in increased production of intracellular reactive oxygen species (ROS) depending on p53, which subsequently triggered the mitochondrial apoptotic pathway. Using a xenograft model in nude mice, we showed that silencing NFBD1 also significantly inhibited tumor growth and led to apoptosis. Taken together, our data suggest that inhibition of NFBD1 in NPC could be therapeutically useful.

Key words: Nasopharyngeal carcinoma (NPC); NFBD1/MDC1; Apoptosis; Reactive oxygen species (ROS); Mitochondrial

Address correspondence to Guohua Hu, Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing 400016, P.R. China. Tel: +86-23-89012945; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 137-145, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14732772150262
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

MicroRNA-92a Promotes Cell Proliferation in Cervical Cancer via Inhibiting p21 Expression and Promoting Cell Cycle Progression

Zhiying Su,*1 Hua Yang,†1 Min Zhao,‡ Yanlong Wang,* Guoyi Deng,* and Ruixin Chen*

*Department of Gynecology, Xiamen Maternal and Child Health Care Hospital, Xiamen, Fujian, P.R. China
†Department of Obstetrics and Gynecology VIP, Xiamen Maternal and Child Health Care Hospital, Xiamen, Fujian, P.R. China
‡Department of Gynecology and Obstetrics, First Affiliated Hospital of Xiamen University, Xiamen, Fujian, P.R. China

MicroRNA-92a (miR-92a) generally plays a promoting role in human cancers, but the underlying mechanism in cervical cancer remains unclear. Here we studied the expression and clinical significance of miR-92a in cervical cancer, as well as the regulatory mechanism in the proliferation of cervical cancer cells. Our data indicated that miR-92a was significantly upregulated in cervical cancer tissues compared to their matched adjacent nontumor tissues (ANTs), and the increased miR-92a levels were significantly associated with a higher grade, lymph node metastasis, and advanced clinical stage in cervical cancer. In vitro study revealed that inhibition of miR-92a led to a significant reduction in the proliferation of HeLa cells via induction of cell cycle arrest at the G1 stage. In contrast, overexpression of miR-92a markedly promoted the proliferation of HeLa cells by promoting cell cycle progression. Further investigation revealed that miR-92a has a negative effect on protein levels, but not the mRNA levels, of p21 in HeLa cells, suggesting that p21 is a direct target of miR-92a. Overexpression of p21 eliminated the promoting effects of miR-92a on the proliferation and cell cycle progression of HeLa cells. However, knockdown of p21 reversed the suppressive effects of miR-92a downregulation on HeLa cell proliferation and cell cycle progression. Moreover, p21 was significantly downregulated in cervical cancer tissues compared to ANTs, suggesting that the increased expression of miR-92a may contribute to the decreased expression of p21, which further promotes cervical cancer growth. In conclusion, our study demonstrates that miR-92a promotes the proliferation of cervical cancer cells via inhibiting p21 expression and promoting cell cycle progression, highlighting the clinical significance of miR-92a in cervical cancer.

Key words: Cervical cancer; MicroRNA-92a (miR-92a); Proliferation; Cell cycle; p21

1These authors provided equal contribution to this work.
Address correspondence to Min Zhao, Department of Gynecology and Obstetrics, First Affiliated Hospital of Xiamen University, No. 55 Zhenhai Road, Xiamen, Fujian 3610003, P.R. China. Tel: +86-592-2137275; Fax: +86-592-2137275; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 147-154, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14732772150505
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Overexpression of MicroRNA-27b Inhibits Proliferation, Migration, and Invasion via Suppression of MET Expression

Hui Zhou,*† Yanglin Liu,† Ling Xiao,‡ Zhengmao Hu,* and Kun Xia*§

*The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, P.R. China
†The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, P.R. China
‡Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, P.R. China
§Key Laboratory of Medical Information Research, Central South University, Changsha, P.R. China

MicroRNA-27b (miR-27b) was recently found to be significantly downregulated in different human cancers. However, evidence of the function of miR-27b in non-small cell lung cancer (NSCLC) remains limited. In this study, we aimed to investigate novel miR-27b-mediated targets or signaling pathways associated with the tumorigenesis and metastasis of NSCLC. Real-time (RT) PCR was performed to examine miR-27b expression in NSCLC specimens. MTT assay, wound-healing assay, and Transwell assay were used to determine cell proliferation, migration, and invasion. Our data indicated that the miR-27b levels were significantly decreased in NSCLC specimens and cell lines (SK-MES-1, H358, H460, A549, and H1229) when compared to matched normal adjacent tissues and normal human lung epithelial cell lines, respectively. Restoration of miR-27b significantly inhibited the proliferation, migration, and invasion of A549 cells. We then conducted in silico analysis and luciferase reporter gene assay and identified MET, a receptor tyrosine kinase, as a direct target of miR-27b in NSCLC cells. Moreover, overexpression of MET rescued the suppressive effect of miR-27b on the proliferation, migration, and invasion of A549 cells, suggesting that MET acts as a downstream effecter of miR-27b in NSCLC cells. In summary, our study identified a novel miR-27b/MET signaling pathway involved in the cell proliferation, migration, and invasion of NSCLC, and identification of miR-27b-mediated novel signaling pathways may help reveal the molecular mechanism underlying the development and malignant progression of this disease.

Key words: Non-small cell lung cancer (NSCLC); MicroRNA-27b (miR-27b); Tumor suppressor; MET; Oncogene

Address correspondence to Professor Kun Xia, The State Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Xiangya Road 110, Changsha, Hunan 410008, P.R. China. Tel: +86-731-84805357; Fax: +86-731-84478152; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 155, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X14811155525280
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

ERRATUM

The follow was originally published in Volume 24, Number 5, pages 353–360 (DOI: http://dx.doi.org/10.3727/096504016X14685034103275). The information that Min Zhao and Zhiying Su provided equal contribution was not included in the original article, so the corrected information is shown below.

Suppressive Role of MicroRNA-148a in Cell Proliferation and Invasion in Ovarian Cancer Through Targeting Transforming Growth Factor-b-Induced 2

Min Zhao,*1 Zhiying Su,†1 Shiyang Zhang,‡ Liangjin Zhuang,§ Yudi Xie,* and Xiaodong Li*

*Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
†Department of Obstetrics, Maternal and Child Health Hospital of Xiamen City, Xiamen, Fujian, China
‡Department of Hospital Infection-Control, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
§Early cancer screening center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China

Ovarian cancer (OC) is one of the most common gynecological malignancies. MicroRNAs (miRs) play a crucial role in the development and progression of OC, but the underlying mechanism remains largely unclear. Our study investigated the regulatory role of miR-148a in OC cell proliferation and invasion. We found that miR-148a was significantly downregulated in OC tissues compared to their matched adjacent nontumor tissues. In addition, its expression was also reduced in OC cell lines (SKOV3, ES-2, OVCAR, and A2780) compared to normal ovarian epithelial cells. Overexpression of miR-148a caused a significant decrease in OC cell proliferation and invasion, as well as reduced MMP9 protein levels. Transforming growth factor-b-induced 2 (TGFI2) was further identified as a target gene of miR-148a, and its protein expression was downregulated in OC cells after miR-148a overexpression. Restoration of TGFI2 attenuated the suppressive effects of miR-148a on OC cell proliferation and invasion. Moreover, we found that TGFI2 was remarkably upregulated in OC tissues when compared with their matched adjacent nontumor tissues, and observed a reverse correlation between miR-148a and TGFI2 expression in OC tissues. On the basis of these findings, we suggest that miR-148a inhibits OC cell proliferation and invasion partly through inhibition of TGFI2. Therefore, our study highlights the importance of the miR-148a/TGFI2 axis in the malignant progression of OC.

Key words: Ovarian cancer (OC); MicroRNAS (miRs); Transforming growth factor-b-induced 2 (TGFI2); Proliferation; Invasion

1These authors provided equal contribution to this work.
Address corresponding to Min Zhao, Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, Fujian, China. Tel: +86-592-2137292; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it