Oncology Research 26(7) Abstracts

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Oncology Research, Vol. 26, pp. 987-996, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15140534417184
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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MicroRNA-379 Suppresses Cervical Cancer Cell Proliferation and Invasion by Directly Targeting V-crk Avian Sarcoma Virus CT10 Oncogene Homolog-Like (CRKL)

Xi Shi,*1 Xiao Xiao,†1 Na Yuan,* Shili Zhang,* Fukang Yuan,‡ and Xiaohong Wang§

*Institute of Audiology and Balance Science, Xuzhou Medical University, Xuzhou, P.R. China
†Reproductive Center, Wuxi Maternal and Child Health-Care Hospital, Wuxi, P.R. China
‡Department of Vascular Surgery, XuZhou Central Hospital, Xuzhou, P.R. China
§Department of Obstetrics and Gynecology, Chinese PLA 101 Hospital, Wuxi, P.R. China

Cervical cancer is the fourth most common malignancy among females worldwide. MicroRNA-379 (miR-379) is aberrantly expressed in multiple human cancer types. However, the expression pattern, roles, and detailed regulatory mechanisms of miR-379 in cervical cancer remain unknown. In this study, we found that miR-379 expression was downregulated in cervical cancer tissues and cell lines. Low miR-379 expression was correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and distant metastasis. Additionally, miR-379 overexpression suppressed the proliferation and invasion of cervical cancer cells. Furthermore, V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) was identified as a direct target of miR-379 in cervical cancer. CRKL was upregulated in cancer tissues and negatively correlated with miR-379 expression. Moreover, restored CRKL expression rescued the inhibitory effects of miR-379 overexpression on cell proliferation and invasion. In conclusion, miR-379 may serve as a tumor suppressor in cervical cancer by directly targeting CRKL. Restoring miR-379 expression may be an effective strategy for the treatment of cervical cancer.

Key words: Cervical cancer; MicroRNA-379 (miR-379); Proliferation; Invasion; V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL)

1These authors provided equal contribution to this work.
Address correspondence to Xiaohong Wang, Department of Obstetrics and Gynecology, Chinese PLA 101 Hospital, No. 101 Xingyuan North Road, Wuxi 214044, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Fukang Yuan, Department of Vascular Surgery, XuZhouCentral Hospital, No. 199 Jiefang Road, Xuzhou 221009, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 997-1003, 2018
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DOI: https://doi.org/10.3727/096504017X
15140544654946
E-ISSN 1555-3906
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Targeted Silencing of Kim-1 Inhibits the Growth of Clear Cell Renal Cell Carcinoma Cell Line 786-0 In Vitro and In Vivo

Jianping Xu, Liguo Sun, Wei Sun, Jianhai Tian, and Huaiyuan Guo

Department of Urology, Tumor Hospital of Linyi City, Lanshan, Linyi, Shandong, P.R. China

To investigate the effect of
Kim-1 on 786-0 cells in vivo and in vitro, several experiments such as quantitative real-time PCR, Western blot, MTT, colony formation, and flow cytometry were performed to evaluate the biological behavior of 786-0 cells treated with Kim-1 siRNA. Furthermore, the tumor xenograft model was applied to BALB/c nude mice to assess the effect of Kim-1 silencing. Lentivirus-mediated RNAi effectively silenced Kim-1 in 786-0 cells. Kim-1 knockdown significantly inhibited the proliferation and colony formation ability of 786-0 cells (p < 0.01). The cell cycle of 786-0 cells was arrested in the G0/G1 phase (p < 0.01). Early and late apoptosis were significantly increased in the Kim-1 siRNA cells (p < 0.01). In addition, growth of 786-0 cells was significantly inhibited in the Kim-1-silenced mice. In conclusion, knockdown of Kim-1 inhibits the growth of 786-0 cells in vitro and in vivo, indicating that Kim-1 could be used as a potential target for clear cell renal cell carcinoma therapy.

Key words: Oxaliplatin; Kidney injury molecule-1 (Kim-1); Clear cell renal cell carcinoma; RNA interference; Proliferation

Address correspondence to Wei Sun, Department of Urology, Tumor Hospital of Linyi City, 6 East Lingyuan Road, Lanshan, Linyi, Shandong 276001, P.R. China. Tel: 0539-8121810; Fax: 0539-8121810; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 997-1014, 2018
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DOI: https://doi.org/10.3727/096504017X
15144755633680
E-ISSN 1555-3906
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Downregulation of MicroRNA-135 Promotes Sensitivity of Non-Small Cell Lung Cancer to Gefitinib by Targeting TRIM16

Ning Wang*1 and Tingting Zhang†1

*Department of Thoracic Surgery, Shengli Oilfield Central Hospital, Dongying, P.R. China
†Department of Oncology, Shengli Oilfield Central Hospital, Dongying, P.R. China

Personalized treatment targeting the epidermal growth factor receptor (EGFR) may be a promising new treatment of non-small cell lung cancer (NSCLC). Gefitinib, a tyrosine kinase inhibitor, is the first drug for NSCLC, which unfortunately easily leads to drug resistance. Our study aimed to explore the functional role of microRNA (miR)-135 in the sensitivity to gefitinib of NSCLC cells. Expression of miR-135 in normal cells and NSCLC cells was assessed, followed by the effects of abnormally expressed miR-135 on cell viability, migration, invasion, apoptosis, sensitivity to gefitinib, and the expression levels of adhesion molecules and programmed death ligand 1 (PD-L1) in H1650 and H1975 cells. Next, the possible target gene of miR-135 was screened and verified. Finally, the potential involvement of the JAK/STAT signaling pathway was investigated. Expression of miR-135 was upregulated in NSCLC cells, and miR-135 silencing repressed cell viability, migration, and invasion, but increased cell apoptosis and sensitivity to gefitinib. E-cadherin and
β-catenin were significantly upregulated, but PD-L1 was downregulated by the silencing of miR-135. Subsequently, tripartite-motif (TRIM) 16 was screened and verified to be a target gene of miR-135, and miR-135 suppression was shown to function through upregulation of TRIM16 expression. Phosphorylated levels of the key kinases in the JAK/STAT pathway were reduced by silencing miR-135 by targeting TRIM16. In conclusion, miR-135 acted as a tumor promoter, and its suppression could improve sensitivity to gefitinib by targeting TRIM16 and inhibition of the JAK/STAT pathway.

Key words: Non-small cell lung cancer (NSCLC); miR-135; Sensitivity to gefitinib; TRIM16; JAK/STAT pathway

1These authors provided equal contribution to this work.
Address correspondence to Tingting Zhang, Department of Oncology, Shengli Oilfield Central Hospital, No. 31 Jinan Road, Dongying 257000, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1015-1022, 2018
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DOI: https://doi.org/10.3727/096504018X
15151486241153
E-ISSN 1555-3906
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The Downregulation of miR-200c Promotes Lactate Dehydrogenase A Expression and Non-Small Cell Lung Cancer Progression

Wei Lei,1 Wang Kang,1 Yang Nan, Zhang Lei, Li Zhongdong, Li Demin, Sun Lei, and Huang Hairong

Department of Cardiothoracic Surgery, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, P.R. China

This study was aimed to investigate the function and mechanism of microRNA-200c (miR-200c) in the progression of non-small cell lung cancer (NSCLC). A total of 76 patients diagnosed as having NSCLC were enrolled in this study. The expression level of miR-200c in NSCLC tissues and cell lines was investigated using the quantitative real-time polymerase chain reaction (RT-qPCR) method. We found that the expression of miR-200c was significantly reduced in NSCLC tissues and cell lines compared with normal lung tissues and the human bronchial epithelial cell line. Overexpression of miR-200c using the miR-200c mimic significantly suppressed cell proliferation and migration of NSCLC cell lines. The results of the luciferase reporter assay identified lactate dehydrogenase A (LDHA) as a direct target of miR-200c. The expression of LDHA was shown to be suppressed in NSCLC cell lines with miR-200c mimic transfection. Furthermore, the transfection of small interfering RNA (siRNA) targeting LDHA suppressed the proliferation and migration of NSCLC cell lines. In summary, our results presented in this study suggested that miR-200c was able to inhibit the proliferation and migration of NSCLC cells by downregulating LDHA. Therefore, miR-200c may be considered as a potential candidate for the treatment of NSCLC.

Key words: miR-200c; Non-small cell lung cancer (NSCLC); Lactate dehydrogenase A (LDHA); Cell proliferation; Cell migration

1These authors provided equal contribution to this work.
Address correspondence to Sun Lei, Department of Cardiothoracic Surgery, Nanjing Jinling Hospital, Nanjing University School of Medicine, No. 305 Zhongshan Dong Road, Gulou District, Nanjing, Jiangsu 210002, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Huang Hairong, Department of Cardiothoracic Surgery, Nanjing Jinling Hospital, Nanjing University School of Medicine, No. 305 Zhongshan Dong Road, Gulou District, Nanjing, Jiangsu 210002, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1023-1029, 2018
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DOI: https://doi.org/10.3727/096504018X
15151515028670
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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miR-143 Inhibits Cell Proliferation of Gastric Cancer Cells Through Targeting GATA6

Mao Guoping,* Liu Ran,and Qin Yanru*

*Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
Department of Rheumatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China

Recent studies have suggested that the dysregulation of microRNAs (miRNAs) plays a critical role in the progression of human cancers, including gastric cancer (GC). miR-143 had been reported to function as a tumor suppressor in GC. However, the exact molecular mechanism of how miR-143 participates in GC progression remains to be determined. In this present study, we revealed that the expression of miR-143 was significantly downregulated in human GC tissues and cell lines compared with normal tissues and a normal gastric epithelium cell line. In addition, upregulation of the expression of miR-143 in a GC cell line inhibited cell proliferation and induced cell cycle arrested in the G0/G1
phase. Furthermore, GATA6 was identified as a direct target of miR-143 in GC using the luciferase reporter assay. Upregulation of miR-143 inhibited the expression of GATA6 in GC cell lines. Moreover, the overexpression of GATA6 could attenuate the effect of miR-143 on cell proliferation in the GC cell lines. Collectively, these data indicated that miR-143 plays a tumor suppressor role partly through regulating the expression of GATA6 in GC. Therefore, targeting miR-143 may be a novel therapeutic method for GC.

Key words: miR-143; Gastric cancer (GC); GATA-binding factor 6 (GATA6); Cell proliferation; Cell cycle

Address correspondence to Professor Qin Yanru, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No 1 Jianshe Road, Erqi District, Zhengzhou, Henan 450052, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1031-1036, 2018
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DOI: https://doi.org/10.3727/096504018X
15151523767752
E-ISSN 1555-3906
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A Retrospective Comparison of the Clinical Efficacy of GefitinibErlotinib, and Afatinib in Japanese Patients With Non-Small Cell Lung Cancer

Atsushi Fujiwara,* Masamichi Yoshida,* Hajime Fujimoto,† Hiroki Nakahara,† Kentaro Ito,‡ Kota Nishihama,§ Taro Yasuma,§ Osamu Hataji,‡ Osamu Taguchi,¶ Corina N. D’Alessandro-Gabazza,§ Esteban C. Gabazza,§ and Tetsu Kobayashi†

*Department of Respiratory Medicine, Mie Prefectural General Medical Center, Yokkaichi, Mie, Japan
†Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Mie, Japan
‡Respiratory Center, Matsusaka Municipal Hospital, Mie, Japan
§Department of Immunology, Mie University Graduate School of Medicine, Mie, Japan
¶Mie University Center for Physical and Mental Health, Tsu, Mie, Japan

Tyrosine kinase inhibitors (TKIs) are very effective against non-small cell lung cancer (NSCLC) caused by epidermal growth factor receptor (EGFR) mutation. Before the approval of osimertinib in March 2016, there were only three available EGFR TKIs (gefitiniberlotinib, and afatinib) for the therapy of NSCLC in Japan. Osimertinib can be indicated only against T790M+
lung cancer as a second-line therapy. However, whether gefitiniberlotinib, or afatinib is most appropriate as a first-line therapy is still a controversial issue. The aim of this study was to compare the effectiveness of gefitiniberlotinib, and afatinib. We retrospectively reviewed the records of 310 patients with the diagnosis of EGFR mutation-associated NSCLC including 147 patients treated with EGFR TKIs. Time to treatment failure and overall survival were evaluated. There were no significant differences in time to treatment failure (gefitinib: 9.2 months; erlotinib: 9.8 months; afatinib: 13.1 months) and overall survival (gefitinib: 27.3 months; erlotinib: 29.3 months; afatinib data not available) among NSCLC patients treated with the three different EGFR TKIs. Subgroup analysis showed that smoking status has a significant influence on both time to treatment failure and overall survival. In conclusion, this study showed comparable clinical efficacy of gefitiniberlotinib, and afatinib in Japanese patients with NSCLC.

Key words: GefitinibErlotinibAfatinib; Non-small cell lung cancer (NSCLC); Epidermal growth factor receptor (EGFR) mutation; Adenocarcinoma; Japanese population

Address correspondence to Esteban C Gabazza, M.D., Ph.D., Department of Immunology, Mie University School of Medicine, Edobashi 2-174, Tsu-city, Mie 514-8507, Japan. Tel: +81 59 231 5037; Fax: +81 59 231 5225; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1037-1046, 2018
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DOI: https://doi.org/10.3727/096504017X
15144748428127
E-ISSN 1555-3906
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Long Noncoding RNA CAT104 Promotes Cell Viability, Migration, and Invasion in Gastric Carcinoma Cells Through Activation of MicroRNA-381-Inhibiting Zinc Finger E-box-Binding Homeobox 1 (ZEB1) Expression

Gang Yuan, Jingzi QuanDongfang Dong, and Qunying Wang

Department of Gastroenterology, 401 Hospital of People’s Liberation Army, Qingdao, P.R. China

Gastric carcinoma (GC) remains the second leading cause of cancer-related deaths worldwide. Good biomarkers are of paramount importance for GC therapy. This study aimed to assess the role of long noncoding RNA (lncRNA) CAT104 in GC. We found that CAT104 was highly expressed in human GC NCI-N87, SGC7901, BGC823, BGC803, and AGS cells. Suppression of CAT104 decreased NCI-N87 cell viability, migration, and invasion, but promoted apoptosis. CAT104 knockdown enhanced the expression of microRNA-381 (miR-381) expression in NCI-N87 cells. miR-381 participated in the regulatory effects of CAT104 on NCI-N87 cell viability, migration, invasion, and apoptosis. Zinc finger E-box-binding homeobox 1 (ZEB1) was identified as a direct target of miR-381. Overexpression of ZEB1 reversed the miR-381 mimic- induced cell viability, migration, and invasion inhibition. Suppression of ZEB1 reversed the miR-381 inhibitor-induced activation of the c-Jun N-terminal kinase (JNK) pathway and Wnt/
β-catenin signaling pathways in NCI-N87 cells. In conclusion, CAT104 might function as an oncogenic factor in GC cells via regulating the expression of miR-381 and ZEB1.

Key words: Long noncoding RNA CAT104; Gastric carcinoma (GC); MicroRNA-381; Zinc finger E-box-binding homeobox 1 (ZEB1); c-Jun N-terminal kinase (JNK) pathway; Wnt/β-catenin pathways

Address correspondence to Qunying Wang, Department of Gastroenterology, 401 Hospital of People’s Liberation Army, No. 22 Minjiang Road, Shinan District, Qingdao 266071, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1047-1053, 2018
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DOI: https://doi.org/10.3727/096504018X
15152037713570
E-ISSN 1555-3906
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Expression and Function of Long Noncoding RNA NONHSAT129183 in Papillary Thyroid Cancer

Jian Ding,* Fuqing Wang,† Tiangang Xiang,‡ and Meng Qiao§

*Department of General Surgery, The Fourth People’s Hospital of Ji’nanJi’nan, Shandong Province, P.R. China
†Department of Burn and Plastic Surgery, Binzhou People’s Hospital, Binzhou, Shandong Province, P.R. China
‡Department of General Surgery, The Second People’s Hospital of DongyingDongying, Shandong Province, P.R. China
§Department of Dermatology, Qilu Hospital of Shandong University, Ji’nan, Shandong Province, P.R. China

The aberrant expression of long noncoding RNAs (lncRNAs) is implicated in cancer development and progression. This study was aimed to investigate the expression and clinical significance of lncRNA NONHSAT129183 in papillary thyroid cancer (PTC), and to explore its roles in PTC cell proliferation, migration, and invasion. Our results demonstrate that lncRNA NONHSAT129183 is upregulated in human PTC tissues when compared with that in adjacent noncancerous thyroid tissue. Moreover, its expression is correlated with tumor size, lymph node metastasis, and TNM stage in PTC patients. lncRNA NONHSAT129183 silencing also significantly suppressed cell proliferation, migration, and invasion in PTC cell lines. In conclusion, our results suggest that lncRNA NONHSAT129183 plays a critical role in the regulation of PTC cell proliferation, migration, and invasion, providing new insights into PTC pathogenesis.

Key words: Papillary thyroid cancer (PTC); Long noncoding RNAs (lncRNAs); lncRNA NONHSAT129183; Proliferation; Migration; Invasion

Address correspondence to Meng Qiao, Department of Dermatology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Ji’nan, 250031, Shandong 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. 26, pp. 1055-1062, 2018
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DOI: https://doi.org/10.3727/096504018X
15152056890500
E-ISSN 1555-3906
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MicroRNA-519d-3p Inhibits Proliferation and Promotes Apoptosis by Targeting HIF-2α in Cervical Cancer Under Hypoxic Conditions

Lixia Jiang,*1 Shaohua Shi,†1 Qiaofa Shi,‡ Huijuan Zhang,* Yu Xia,§ and Tianyu Zhong*

*Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, P.R. China
†Department of Information Technology, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, P.R. China
‡Department of Immunology, Medical College of Nanchang University, Nanchang, Jiangxi, P.R. China
§Gannan Medical University, Ganzhou, Jiangxi, P.R. China

HIF-2
α knockdown inhibits proliferation, arrests the cell cycle, and promotes apoptosis and autophagy under hypoxic conditions in cervical cancer. However, the upstream regulatory mechanism of HIF-2α expression is unclear. MicroRNAs (miRNAs) degrade target mRNAs by binding to the 3-untranslated region of mRNAs. In this study, we investigated the role of miRNAs in the regulation of HIF-2α expression in cervical cancer under hypoxic conditions. miRNAs regulating HIF-2α expression were predicted using TargetScan and miRanda and were determined in cervical cancer under hypoxic conditions by qRT-PCR. Additionally, the targeted regulation of HIF-2α by miR-519d-3p was evaluated by Western blot and luciferase reporter assays. Effects of miR-519d-3p and HIF-2α on cell proliferation, cell cycle, and apoptosis were analyzed by CCK-8 and flow cytometry assays, respectively. miR-106a-5p, miR-17-5p, miR-519d-3p, miR-526b-3p, and miR-20b-5p are potentially regulatory miRNAs that bound to the HIF-2α 3-untranslated region as per TargetScan and miRanda predictions. Expression of the five miRNAs was inhibited in HeLa cells under hypoxic conditions compared to normoxic conditions, and the expression of miR-519d-3p was lower than that of other miRNAs. Luciferase reporter assays showed that HIF-2α was a target of miR-519d-3p. Additionally, miR-519d-3p overexpression inhibited cell proliferation, arrested the cell cycle transition from the G1 stage to the S stage, and promoted cell apoptosis under hypoxic conditions in cervical cancer. HIF-2α overexpression partially reversed the effect of miR-519d-3p. In conclusion, miR-519d-3p overexpression suppressed proliferation, inhibited the cell cycle, and promoted apoptosis of HeLa cells by targeting HIF-2α under hypoxic conditions.

Key words: MicroRNAs (miRNAs); Hypoxia-inducible factor-2α (HIF-2α); Cervical cancer; Cell hypoxia

1These authors provided equal contribution to this work.
Address correspondence to Lixia Jiang, Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, 23 Qingnian Road, Ganzhou 341000, Jiangxi, P.R. China. Tel: +86-7978269502; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Tianyu Zhong, Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, 23 Qingnian Road, Ganzhou 341000, Jiangxi, P.R. China. Tel: +86-7978269502; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1063-1072, 2018
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DOI: https://doi.org/10.3727/096504018X
15152072098476
E-ISSN 1555-3906
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Long Noncoding RNA ATB Promotes Proliferation, Migration, and Invasion in Bladder Cancer by Suppressing MicroRNA-126

Xingquan Zhai and Wei Xu

Department of Urology, Zoucheng People’s Hospital, Zoucheng, Shandong, P.R. China

This study aimed to explore the biological functions of long noncoding RNA activated by transforming growth factor-
β (lncRNA-ATB) in bladder cancer cells. For the expressions of lncRNA-ATB, miR-126, and KRAS, T24 cells were transfected with their specific vectors/shRNA or mimic/inhibitor. Then cell viability, migration, invasion, and apoptosis as well as the protein levels of apoptosis-related factors and PI3K/AKT and mTOR signal pathways were measured. The relationships of lncRNA-ATB and miR-126 or miR-126 and KRAS were analyzed by Dual-Luciferase Reporter assay. Functional experiments showed that lncRNA-ATB overexpression significantly promoted cell viability, migration, and invasion in T24 cells. lncRNA-ATBwas a molecular sponge of miR-126 and exerted tumor-promoting effects by downregulation of miR-126. Moreover, KRAS was a direct target of miR-126 and was negatively regulated by miR-126. Finally, overexpression of KRAS increased cell viability, migration, and invasion, as well as activated PI3K/AKT and mTOR signaling pathways in T24 cells. The results revealed that lncRNA-ATB was an oncogene, which promoted cell proliferation, migration, and invasion by regulating miR-126 in bladder cancer. These findings may provide a potential prognostic biomarker and a therapeutic target for bladder cancer.

Key words: Bladder cancer; MicroRNA-126; KRAS; PI3K/AKT/mTOR; Long noncoding RNA activated by transforming growth factor-β (lncRNA-ATB)

Address correspondence to Wei Xu, Department of Urology, Zoucheng People’s Hospital, No. 59, Qianquan Road, Zoucheng, Shandong 273500, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1073-1081, 2018
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DOI: https://doi.org/10.3727/096504017X
15145088802439
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miR-346 Promotes HCC Progression by Suppressing Breast Cancer Metastasis Suppressor 1 Expression

Zhixian Guo,*1 Jingjing Li,*1 Jihong Sun,† Lu Sun,† Yubing Zhou,‡ and Zujiang Yu*

*Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
†Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
‡Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. MicroRNA (miRNA), a class of noncoding single-stranded RNA molecules, is involved in regulating cancer cell proliferation, metastasis, migration, invasion, and apoptosis. We showed that the expression of miR-346 was significantly increased in HCC tissues and cell lines, compared with noncancerous controls, and was associated with poor prognosis. Overexpression of miR-346 promoted proliferation and inhibited apoptosis of SMMC-7721 cells, while knockdown of miR-346 significantly suppressed proliferation and induced apoptosis of HepG2 cells. Then we identified breast cancer metastasis suppressor 1 (BRMS1) as a direct target of miR-346 based on luciferase reporter assays. There was a negative correlation between miR-346 and BRMS1 expression at both the protein and mRNA levels. Furthermore, inhibition of BRMS1 expression reversed the tumor-suppression effects of miR-346 downregulation in HepG2 cells. These results indicate that miR-346 promotes HCC progression by regulating BRMS1 expression.

Key words: MicroRNA-346; Breast cancer metastasis suppressor 1 (BRMS1); Hepatocellular carcinoma (HCC); Proliferation; Migration and invasion

1These authors provided equal contribution to this work.
Address correspondence to Zujiang Yu, M.D., Department of Infectious Disease, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe E Road, Erqi, Zhengzhou, Henan 450052, P.R. China. Tel: +86-0371-67907574; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1083-1091, 2018
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DOI: https://doi.org/10.3727/096504018X
15152085755247
E-ISSN 1555-3906
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Upregulation of Long Noncoding RNA TUG1 Promotes Bladder Cancer Cell Proliferation, Migration, and Invasion by Inhibiting miR-29c

Peng Guo,* Guohui Zhang,*† Jialin Meng,‡ Qian He,* Zhihui Li,† and Yawei Guan†

*Clinical Medical College, The Chinese People’s Liberation Army General Hospital, Anhui Medical University, Hefei, Anhui, P.R. China
†Department of Urologic Surgery, The Chinese People’s Liberation Army General Hospital, Beijing, P.R. China
‡Department of Urologic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P.R. China

Bladder cancer (BC) is one of the leading causes of cancer-related deaths in the world. Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) plays an important role in the development and progression of numerous cancers, including BC. However, the exact role of TUG1 in modulating BC progression is still poorly known. In this study, we found that TUG1 was upregulated and microRNA-29c (miR-29c) was downregulated in BC tissues and cell lines. Overexpression of TUG1 promoted the cell proliferation of T24 and EJ cells, whereas TUG1 knockdown had the opposite effect. Upregulation of TUG1 obviously facilitated the migration and invasion of T24 and EJ cells. In contrast, TUG1 silencing repressed the migration and invasion of T24 and EJ cells. Furthermore, TUG1 knockdown markedly increased the expression of miR-29c in vitro. On the contrary, overexpression of TUG1 remarkably decreased the expression of miR-29c. Transfection with plasmids containing mutant TUG1 has no effect on the expression of miR-29c. There were direct interactions between miR-29c and the binding sites of TUG1. In addition, the inhibitory effects of small interfering RNA specific for TUG1 on BC cell proliferation, migration, and invasion were reversed by downregulation of miR-29c. Collectively, our study strongly demonstrates that TUG1 promotes BC cell proliferation, migration, and invasion by inhibiting miR-29c, suggesting that lncRNATUG1 may be a promising target for BC gene therapy.

Key words: Long noncoding RNA; Taurine-upregulated gene 1 (TUG1); Bladder cancer (BC); MicroRNA 29c (miR-29c)

Address correspondence to Professor Guohui Zhang, Department of Urologic Surgery, The Chinese People’s Liberation Army General Hospital, No. 5 Dongsishitiao Road, Dongcheng District, Beijing 100700, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1093-1102, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15154112497142
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


MicroRNA-212 Targets Mitogen-Activated Protein Kinase 1 to Inhibit Proliferation and Invasion of Prostate Cancer Cells

Bo Hu,* Xunbo Jin,* and Jianbo Wang†

*Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, P.R. China
†Department of Oncology, Qilu Hospital of Shandong University, Shandong, P.R. China

Prostate cancer (PCa) is the second most commonly diagnosed malignancy and the fifth leading cause of cancer-related deaths in males worldwide. MicroRNAs (miRNAs) may serve as important regulators in PCa occurrence and development. Therefore, understanding the expression and functions of PCa-related miRNAs may be beneficial for the identification of novel therapeutic methods for patients with PCa. In this study, miRNA-212 (miR-212) was evidently downregulated in PCatissues and several PCa cell lines. Functional assays showed that the resumption of miR-212 expression attenuated cell proliferation and invasion and increased the apoptosis of PCa. In addition, mitogen-activated protein kinase 1 (MAPK1), a well-known oncogene, was identified as a novel target of miR-212 in PCa, as confirmed by bioinformatics, luciferase reporter assay, qRT-PCR, and Western blot analysis. Furthermore, MAPK1 expression was upregulated in PCa tissues and inversely correlated with miR-212 expression. Rescue experiments also demonstrated that restored MAPK1 expression reversed the tumor-suppressing effects of miR-212 on PCa cell proliferation, invasion, and apoptosis. In conclusion, miR-212 may exert tumor-suppressing roles in PCa by regulating MAPK1 and could be a novel therapeutic target for treatment of patients with this malignancy.

Key words: Prostate cancer; MicroRNA-212; Proliferation; Invasion; Apoptosis; Mitogen-activated protein kinase 1 (MAPK1)

Address correspondence to Xunbo Jin, Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, No. 324, Jingwu Road, Jinan, Shandong 250012, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1103-1111, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15164123839400
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


Let-7c Inhibits the Proliferation, Invasion, and Migration of Glioma Cells via Targeting E2F5

Mengyi Huang and Xin Gong

Department of Neurosurgery, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha City, P.R. China

As a member of the miRNA family, let-7c has been identified as a tumor suppressor in many cancers. However, the molecular biological function of let-7c in glioma has not been elucidated. The aim of this study was to explore let-7c expression levels and evaluate its function in glioma cells. We first measured the expression of let-7c in four glioma cell lines and a normal cell line by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and the results showed that let-7c was downregulated in glioma cells. By applying gain-of-function and loss-of-function assays, the experiments suggested that dysregulation of let-7c could obviously affect cell proliferation, metastasis, and invasion. Based on online bioinformatics analysis and Dual-Luciferase Reporter assays, we found that E2F5 was a target gene of let-7c and contributed to the function of let-7c in glioma cells. Our investigations indicated that loss of let-7c contributed to the progression of glioma cells.

Key words: Glioma; let-7c; E2F transcription factor 5 (E2F5); Proliferation; Invasion; Migration

Address correspondence to Xin Gong, Department of Neurosurgery, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61, the West Liberation Road, Changsha City, 410005, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1113-1121, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15166199939341
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


miR-522-3p Promotes Tumorigenesis in Human Colorectal Cancer via Targeting Bloom Syndrome Protein

Feng Shuai,* Bo Wang,† and Shuxiao Dong‡

*Department of Gastroenterology, Eastern District of Linyi People’s Hospital, Linyi, Shandong, P.R. China
†Department of Pediatrics, Chinese Medicine Hospital in Linyi City, Linyi, Shandong, P.R. China
‡Department of Gastrointestinal Surgery, Linyi People’s Hospital, Linyi, Shandong, P.R. China

miR-522-3p is known to degrade bloom syndrome protein (BLM) and enhance expression of other proto-oncogenes, leading to tumorigenesis. This study aimed to investigate the molecular mechanisms of miR-522-3p in human colorectal cancer (CRC) cells. Expressions of miR-522-3p in CRC and adjacent tissues, as well as in normal human colon epithelial cell line (FHC) and five CRC cell lines, were detected. Human CRC cell lines, HCT-116 and HT29, were transfected with miR-522-3p mimic, inhibitor, or scrambled controls. Then cell viability, apoptosis, cell cycle progression, and the expressions of c-myc, cyclin E, CDK2, and BLM were assessed. It was found that miR-522-3p was highly expressed in CRC tissues when compared to adjacent nontumor tissues and was highly expressed in CRC cell lines when compared to FHC cells. miR-522-3p overexpression promoted cell viability, reduced apoptotic cell rate, arrested more cells in the S phase, and upregulated c-myc, cyclin E, and CDK2 expression. BLM was a target gene of miR-522-3p, and miR-522-3p suppression did not exert antiproliferative and proapoptotic activities when BLM was silenced. These findings demonstrate that miR-522-3p upregulation negatively regulates the expression of BLM, with upregulation of c-myc, CDK2, and cyclin E, and thereby promoting the proliferation of human CRC cells.

Key words: MicroRNAs; Colorectal neoplasms; Bloom syndrome

Address correspondence to Shuxiao Dong, Department of Gastrointestinal Surgery, Linyi People’s Hospital, No. 27 Jiefang Road, Lanshan District, Linyi 276000, Shandong, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1123-1131, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15166223632406
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


Phosphoglycerate Mutase 1 (PGAM1) Promotes Pancreatic Ductal Adenocarcinoma (PDAC) Metastasis by Acting as a Novel Downstream Target of the PI3K/Akt/mTOR Pathway

Xinlu Liu, Xiaodong Tan, Peng Liu, Yunhao Wu, Songying Qian, and Xiaobo Zhang

First Department of General Surgery, Shengjing Hospital of China Medical University, Heping District, Shenyang, Liaoning, P.R. China

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors known, with an overall 5-year survival rate of less than 6% due to early local invasion and distant metastasis. Exploring suitable therapeutic targets associated with invasion and metastasis is required for improving the prognosis of PDAC. In this study, we investigated the role of the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) in PDAC. PGAM1 expression was examined in tissue samples of 54 PDAC patients using immunohistochemistry, and the correlation between clinicopathological expression and PGAM1 expression was determined. A survival curve was generated using the Kaplan–Meier method. After silencing PGAM1 by siRNA in pancreatic cancer cell lines Aspc-1 and Panc-1, the changes in proliferation, migration, and invasion, and signal pathways were determined. In this study, the expression of PGAM1 was found positively related to poor differentiation, metastasis, advanced clinical stage, and poor survival rate. Silencing PGAM1 decreased the proliferation of Aspc-1 and Panc-1 cells with an S phase arrest, but without influencing cell apoptosis. Migration and invasion also decreased significantly, independent of proliferation. PGAM1 was also found to promote EMT of PDAC cell lines by regulating the Wnt/
β-catenin pathway. PGAM1 itself was modulated by the PI3K/Akt/mTOR pathway as a novel downstream target and has a positive mutual regulation with HIF-1α. This study indicates that PGAM1 is closely associated with clinical metastasis and poor prognosis of PDAC. PGAM1 is considered as a potential therapeutic target in PDAC metastasis.

Key words: Pancreatic ductal adenocarcinoma (PDAC); Phosphoglycerate mutase 1 (PGAM1); Metastasis; Wnt/β-catenin; PI3K/Akt/mTOR; Hypoxia-inducible factor 1α (HIF-1α)

Address correspondence to Xiaodong Tan, First Department of General Surgery, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning, P.R. China. Tel: +86-024-96615; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 1133-1142, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504018X
15168461629558
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


Matrine Inhibits Neuroblastoma Cell Proliferation and Migration by Enhancing Tribbles 3 Expression

Xiaowei Shen,*1 Jianping Huang,†1 Gang Liu,† Hao Zhang,† Xiwei Zhang,† Xiancheng Kong,† and Lei Du†

*Department of General Surgery, the Affiliated Zhongshan Hospital of Fudan University, Qingpu Branch, Shanghai, P.R. China
†Department of General Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China

Neuroblastoma is a major contributor of cancer-specific mortality. Although remarkable enhancement has been achieved in the treatment of neuroblastoma in patients with early stage disease, limited progress has been made in the treatment of patients with high-risk neuroblastoma. Thus, innovative approaches are required to achieve further improvements in neuroblastoma patient survival outcomes. The major alkaloid obtained from
Sophora flavescens Aitmatrine, has been shown to counteract malignancy in various kinds of cancers. In the current study, we evaluated the effects of matrine on the migration and proliferation of neuroblastoma cells. Cell cycle analysis coupled with Transwell and wound healing experiments showed that matrinetriggers G2/M cell cycle arrest and suppresses neuroblastoma migration. This effect of matrine is due to upregulation of TRB3 expression followed by inhibition of the PI3K/AKT activation. Consistent with the in vitro data, growth of xenograft cancer was also suppressed by matrine. Our results indicate that matrine inhibits neuroblastoma cell proliferation and migration by enhancing TRB3 expression, suggesting that matrine may serve as a promising agent for the treatment of neuroblastoma.

Key words: Neuroblastoma; Matrine; Tribbles 3 (TRB3); Proliferation; Migration

1These authors provided equal contribution to this work and are co-first authors.
Address correspondence to Lei Du, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P.R. China. Tel: 86-021-53827296; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it