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)

Abstract

BackgroundIn recent years, the incidence of gastric cancer (GC) has been increasing worldwide. Emerging evidence shows that microRNAs (miRs) may be involved in the pathogenesis of GC. Thus, this study explored the mediatory role of miR-495 in GC chemosensitivity, and investigated the mechanism by which it affects the biological behaviors of GC cells via the mTOR signaling pathway.Material/MethodsAfter 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 was assessed by flow cytometry.ResultsWe found higher positive rates of ERBB2 and mTOR and decreased expression of miR-495 in GC tissues and showed that ERBB2 is the target gene of miR-495. Furthermore, we determined that overexpression of miR-495 and silencing of ERBB2 enhanced GC cell chemosensitivity and apoptosis, but inhibited GC cell proliferation. We also found that the effect of miR-495 inhibition was lost when ERBB2 was suppressed.ConclusionsThe key findings of our study demonstrate that the miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2. The study provides reliable evidence supporting the use of miR-495 as a novel potential target in the chemotherapy of GC.

miR‑876‑5p suppresses breast cancer progression through targeting TFAP2A

“…Evidence has demonstrated that miRNAs initiate or suppress cancer development by regulating cell proliferation, metastasis, apoptosis or differentiation (10). For example, miR-495 regulates the progression of gastric cancer via the mammalian target of rapamycin pathway (11). miR-150 suppresses thyroid cancer development by modulating Ras-related protein Rab-11A/WNT/β-Catenin signaling (12).…”

Genetic Analyses Confirm SNPs in HSPA8 and ERBB2 are Associated with Milk Protein Concentration in Chinese Holstein Cattle

“…HSPA8 is highly involved in many biological processes, including proteasomal degradation [ 35 ], catalyzing protein folding and clathrin uncoating [ 36 ], and other protein networks involved in protein catabolism, protein homeostasis, ubiquitination, carbohydrate metabolism and cell cycle control [ 37 ]. ERBB2 is a member of a family of transmembrane receptor tyrosine kinases involved in the regulation of cellular processes by modulation of several pathways, such as mTOR, MAPK, and PI3K/AKT pathways [ 38 , 39 , 40 ]. In consistent with the present study, the functional role of ERBB2 on milk production traits has been also identified as positional candidate gene for lactation persistency in Canadian Holstein cattle [ 41 ].…”

Non-coding RNA transcripts, incredible modulators of cisplatin chemo-resistance in bladder cancer through operating a broad spectrum of cellular processes and signaling mechanism

“…Consistent with these findings, it was also determined that miR-486–5p combined with cisplatin could induce caspase-9 and -3, as well as p53, while suppressed the anti-apoptotic genes sirtuin 1 (SIRT1), olfactomedin 4 (OLFM4), SMAD4, and Bcl-2. Thus, it can be concluded that miR-486–5p mimic can help cisplatin to exert more efficient apoptotic effects on BC cell [ [92] , [93] , [94] ]. In detail, apoptosis induction caused by concurrent administration of this miRNA mimic and cisplatin chemo drug is primarily regulated through subG1 phase arrest during the cell cycle [ 91 ].…”