miR-590-5p regulates gastric cancer cell growth and chemosensitivity through RECK and the AKT/ERK pathway
Authors Shen B, Yu S, Zhang Y, Yuan Y, Li X, Zhong J, Feng J
Received 20 April 2016
Accepted for publication 3 August 2016
Published 3 October 2016 Volume 2016:9 Pages 6009—6019
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Chiung-Kuei Huang
Peer reviewer comments 4
Editor who approved publication: Dr William Cho
Bo Shen,* Shaorong Yu,* Yan Zhang, Yuan Yuan, Xiaoyou Li, Jian Zhong, Jifeng Feng
Department of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
*These authors contributed equally to this work
Background: The aim of this study was to determine the role of miRNA-590-5p in gastric cancer (GC) progression.
Methods: Quantitative real-time polymerase chain reaction was performed to measure endogenous miR-590-5p levels in GC cells and tissues. Overexpression or knockdown of miR-590-5p in GC cells was performed by transfection with mimics or an inhibitor, respectively. MTT, matrigel transwell, and Western blot assays were used to assess the effects of miR-590-5p on cell proliferation, invasion, chemosensitivity of GC cells, and the AKT pathway, respectively. In silico prediction and luciferase reporter activity were used to identify potential targets of miR-590-5p. A xenograft model was also established to evaluate the function of miR-590-5p in vivo.
Results: The expression of miR-590-5p was significantly increased in GC cells and tissues, and upregulated miR-590-5p was associated with increased tumor size, lymph node metastasis, and poor survival. Overexpression of miR-590-5p promoted cell proliferation and invasion and reduced the sensitivity of GC cells to cisplatin and paclitaxel. In contrast, inhibition of miR-590-5p had the opposite effects on GC cells. RECK was identified as a direct target of miR-590-5p. Knockdown of RECK accelerated cell proliferation and motility and decreased the drug sensitivity. Furthermore, reintroduction of RECK inhibited the oncogenic effects of miR-590-5p by suppressing cell proliferation and invasion and increasing drug sensitivity. We found that the AKT/ERK and STAT3 signaling pathways were activated by miR-590-5p overexpression. The chemoresistance of miR-590-5p was also verified by in vivo analysis.
Conclusion: In summary, we suggest that the miR-590-5p/RECK/AKT axis contributes to GC and may serve as a promising therapeutic target for treatment.
Keywords: miR-590, RECK, invasion, prognosis, AKT pathway, gastric cancer
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