miR-320a modulates cell growth and chemosensitivity via regulating ADAM10 in gastric cancer

Ge,Xiancai; Cui,Haiyan; Zhou,Yanbing; Yin,Deying; Feng,Yuanyuan; Xin,Qun; Xu,Xianhui; Liu,Weijing; Liu,Shanglong; Zhang,Qin

doi:10.3892/mmr.2017.7819

miR-320a modulates cell growth and chemosensitivity via regulating ADAM10 in gastric cancer

Authors:
- Xiancai Ge
- Haiyan Cui
- Yanbing Zhou
- Deying Yin
- Yuanyuan Feng
- Qun Xin
- Xianhui Xu
- Weijing Liu
- Shanglong Liu
- Qin Zhang
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Affiliations: Department of General Surgery, 401 Hospital of People's Liberation Army, Qingdao, Shandong 266000, P.R. China, Department of Oncological Surgery, Anqiu People's Hospital, Weifang, Shandong 261000, P.R. China, Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266555, P.R. China, Department of Officer, 401 Hospital of People's Liberation Army, Qingdao, Shandong 266000, P.R. China
Published online on: October 19, 2017 https://doi.org/10.3892/mmr.2017.7819
Pages: 9664-9670

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Abstract

MicroRNAs (miRNAs) may function as tumor suppressor or onco‑miRNAs and have critical roles in the pathogenesis of gastric cancer (GC). The exact function and mechanism of miRNA (miR)‑320a in GC remains to be elucidated. The present study performed gain‑ and loss‑of‑function analyses by transfecting cells with mimics or inhibitors and subsequently performing colony formation, proliferation and cisplatin‑sensitivity assays. Additionally, in vivo xenograft models were also performed. Bioinformatics algorithms, luciferase reporter activity assay and western blotting were used to predict the potential target of miR‑320a. Additionally, the effect of knockdown or overexpression of ADAM metallopeptidase domain 10 (ADAM10) on cell growth and chemosensitivity was examined. The expression of miR‑320a and ADAM10 was also determined in primary tumors. The present study revealed that the expression of miR‑320a was reduced in GC cells and ectopic miR‑320a expression significantly inhibited cell growth in vitro and in vivo and enhanced the sensitivity of GC cells to cisplatin. ADAM10 was a direct target of miR‑320a in GC. Knockdown of ADAM10 attenuated the proliferative ability of GC cells, and increased the sensitivity of GC cells to cisplatin. The upregulated ADAM10 accelerated cell growth rate and reduced the cisplatin‑sensitivity of cells. Clinically, a significantly negative correlation was identified between the expression of miR‑320a and mRNA levels of ADAM10 in tumors. The findings of the present study suggested that miR‑320a may function as a tumor suppressor in GC progression and potential therapeutic strategies for GC may be based on the miR‑320a/ADAM10 axis.

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