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MicroRNA-320 inhibits invasion and induces apoptosis by targeting CRKL and inhibiting ERK and AKT signaling in gastric cancer cells

Authors Zhao Y, Dong Q, Wang E

Received 27 September 2016

Accepted for publication 17 December 2016

Published 20 February 2017 Volume 2017:10 Pages 1049—1058

DOI https://doi.org/10.2147/OTT.S123324

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Ingrid Espinoza

Yue Zhao, Qianze Dong, Enhua Wang

Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, People’s Republic of China

Abstract: MicroRNA-320 (miR-320) downregulation has been reported in several human cancers. Until now, its expression pattern and biological roles in human cancer remain unknown. This study aims to clarify its clinical expression pattern and biological function in gastric cancers. We found miR-320 level was downregulated in gastric cancer tissues. miR-320 mimic was transfected in SGC-7901 cells with low endogenous expression. miR-320 inhibitor was used in BGC-823 cells with high endogenous expression. We found that miR-320 inhibited SGC-7901 proliferation and invasion, with decreased expression of cyclin D1 and MMP9 at both mRNA and protein levels. We also found that miR-320 mimic downregulated chemoresistance and cell survival of gastric cancer cells when treated with 5-fluorouracil. miR-320 inhibitor displayed the opposite effects in BGC-823 cell line. In addition, we discovered that miR-320 mimic could inhibit AKT and ERK activity. By using luciferase reporter assay, we found that CRKL serves as the target of miR-320. miR-320 mimic downregulated CRKL expression, whereas miR-320 inhibitor upregulated CRKL expression. miR-320 suppressed CRKL-3'-untranslated region reporter intensity in SGC-7901 cells. Furthermore, CRKL depletion abrogated the effects of miR-320. In gastric cancer tissues, we observed a negative correlation between CRKL and miR-320. In conclusion, our study demonstrated that downregulation of miR-320 was closely related with malignant progression of gastric cancer. miR-320 inhibits proliferation, invasion, and chemoresistance through ERK and AKT signaling by targeting CRKL.

Keywords:
gastric cancer, miR-320, CRKL, proliferation, invasion

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