MicroRNA‑383‑5p inhibits the proliferation and promotes the apoptosis of gastric cancer cells by targeting cancerous inhibitor of PP2A

Abstract

The aberrant expression of microRNA (miRNAor miR)-383-5p has been found in numerous types of cancer. However, the function of miR-383-5p in gastric cancer (Gc) remains elusive and requires further investigation. In the present study, the level of miR-383-5p and cancerous inhibitor of PP2A (cIP2A) in Gc cell lines was determined by reverse transcription-quantitative PcR analysis. Gc cell proliferation, apoptosis and cell cycle distribution were determined by the MTT assay and flow cytometry, respectively. The mRNA target of miR-383-5p was identified by dual luciferase activity assay. It was observed that the expression of miR-383-5p was lower and that of cIP2A was higher in Gc cells compared with the GES-1 normal human gastric epithelial cell line. Transfectoin with miR-383-5p mimic significantly inhibited Gc cell proliferation, while it promoted cell apoptosis and G 0 /G 1 arrest by targeting CIP2A. Taken together, the findings of the present study demonstrate that miR-383-5p inhibits Gc cell proliferation and promotes apoptosis and G 0 /G 1 arrest by targeting cIP2A, indicating that targeting miR-383-5p may hold promise as a future therapeutic strategy for patients with Gc. Materials and methodsCell culture. The 293T cell line, the normal human gastric epithelial cell line GES-1, and two Gc cell lines (AGS and HGc-27) were purchased from the American Type culture Collection. The cells were cultured in Dulbecco's modified Eagle's medium (Invitrogen; Thermo Fisher Scientific, Inc.), supplemented with 5% fetal bovine serum (Invitrogen; Thermo

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“…CIP2A inactivates protein phosphatase 2A (PP2A), which reduces the phosphorylation of Akt (protein kinase B) and stabilizes the c-Myc proto-oncogene in tumor cells ( Soofiyani et al, 2017a ). In the miR-383-5p/CIP2A pathway, decreased miR-383-5p expression together with higher CIP2A expression was found in GC cells compared with normal gastric epithelial cells ( Li et al, 2020a ). CIP2A promotes cancer cell proliferation and prevents apoptosis ( Soofiyani et al, 2017b ).…”

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“…According to the mechanism of miRNA regulating the targeted genes, the predicted miRNA should be down-regulated and negatively correlated with MTHFD2 expression in bladder cancer and miR-383-5p met the two required conditions. Previous studies also showed that miR-383-5p suppressed the proliferation and induced the apoptosis in gastric cancer cells [30]. Hence, miR-383-5p was assumed to be the most potential upstream miRNA of MTHFD2.…”

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“…According to the mechanism of miRNA regulating the targeted genes, the predicted miRNA should be down-regulated and negatively correlated with MTHFD2 expression in bladder cancer and miR-383-5p met the two required conditions. Previous studies also showed that miR-383-5p suppressed the proliferation and induced the apoptosis in gastric cancer cells [40]. Hence, miR-383-5p was assumed to be the most potential upstream miRNA of MTHFD2.…”