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27 August 2018 : Clinical Research  

MicroRNA-495 Confers Increased Sensitivity to Chemotherapeutic Agents in Gastric Cancer via the Mammalian Target of Rapamycin (mTOR) Signaling Pathway by Interacting with Human Epidermal Growth Factor Receptor 2 (ERBB2)

Na Li1BC, Mei Han1AB, Ning Zhou1BC, Yong Tang1DE, Xu-Shan Tang1DE*

DOI: 10.12659/MSM.909458

Med Sci Monit 2018; 24: CLR5960-5972

Abstract

BACKGROUND: In recent years, the incidence of gastric cancer (GC) presents is increasing and plagues people worldwide. Emerging evidence shows that microRNAs (miRs) may be involved in the pathogenesis of GC. Thus, this paper aims to explore the mediatory role of miR-495 in GC chemosensitivity, and the mechanism by which it affected the biological behaviors of GC cell via the mTOR signaling pathway.

MATERIAL AND METHODS: After GC and paracancerous tissue collection, the positive rate of ERBB2 and mTOR was evaluated by immunohistochemistry. Subsequently, the expression of miR-495, ERBB2 and mTOR was determined by RT-qPCR and western blot analysis. Next, the targeting relationship between miR-495 and ERBB2 was confirmed by dual-luciferase reporter gene assay. In addition, chemosensitivity and proliferation were detected by MTT assay, and apoptosis by flow cytometry.

RESULTS: We firstly observed that higher positive rate of ERBB2 and mTOR as well as decreased expression of miR-495 were found in GC tissues. Additionally, ERBB2 is the target gene of miR-495. Furthermore, it was determined that overexpressed miR-495 or silencing ERBB2 enhanced GC cells chemosensitivity and apoptosis, but inhibited GC cell proliferation. Besides, we found that the effect of miR-495 inhibition was lost when ERBB2 was suppressed.

CONCLUSIONS: The key findings of our study demonstrate that the miR-495 exerts promoting effects on GC chemosensitivity via the inactivation of mTOR signaling pathway by suppressing ERBB2. The study provides reliable reference for the application of miR-495 as a novel potential target in the chemotherapy of GC.

Keywords: Gastroenterology, Stomach Diseases

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750