Oncotarget

Research Papers:

miR-135a promotes gastric cancer progression and resistance to oxaliplatin

Lin-Hai Yan _, Zhi-Ning Chen, Li -Li, Jia Chen, Wen-E Wei, Xian-Wei Mo, Yu-Zhou Qin, Yuan Lin and Jian-Si Chen

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Oncotarget. 2016; 7:70699-70714. https://doi.org/10.18632/oncotarget.12208

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Abstract

Lin-Hai Yan1, Zhi-Ning Chen2, Li-Li3, Jia Chen4, Wen-E Wei5, Xian-Wei Mo1, Yu-Zhou Qin1, Yuan Lin1, Jian-Si Chen1

1Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China

2Department of Pathology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China

3Department of Pharmacy, The People Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi Zhuang Autonomous Region, China

4Department of Medical Image Center, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China

5Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China

Correspondence to:

Lin-Hai Yan, email: lhyan@gxmu.edu.cn

Keywords: gastric cancer, transcription factor E2F1

Received: March 16, 2016    Accepted: September 13, 2016    Published: September 23, 2016

ABSTRACT

Resistance to oxaliplatin (OXA)-based chemotherapy regimens continues to be a major cause of gastric cancer (GC) recurrence and metastasis. We analyzed GC samples and matched non-tumorous control stomach tissues from 280 patients and found that miR-135a was overexpressed in GC samples relative to control tissues. Tumors with high miR-135a expression were more likely to have aggressive characteristics (high levels of carcino-embryonic antigen, vascular invasion, lymphatic metastasis, and poor differentiation) than those with low levels. Patients with greater tumoral expression of miR-135a had shorter overall survival times and times to disease recurrence. Furthermore, miR-135a, which promotes the proliferation and invasion of OXA-resistant GC cells, inhibited E2F transcription factor 1 (E2F1)-induced apoptosis by downregulating E2F1 and Death-associated protein kinase 2 (DAPK2) expression. Our results indicate that higher levels of miR-135a in GC are associated with shorter survival times and reduced times to disease recurrence. The mechanism whereby miR-135a promotes GC pathogenesis appears to be the suppression of E2F1 expression and Sp1/DAPK2 pathway signaling.


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