MicroRNA-490-3p regulates cell proliferation and apoptosis in gastric cancer via direct targeting of AKT1

Exp Ther Med. 2019 Feb;17(2):1330-1336. doi: 10.3892/etm.2018.7042. Epub 2018 Dec 3.

Abstract

microRNA (miRNA) expression profiles of gastric cancer (GC) and adjacent healthy gastric mucosa tissue were used to search for differentially expressed miRNAs, identifying downregulated miRNA-490-3p in GC. The present study aimed to investigate the cellular function of miRNA-490-3p and its underlying mechanism in the occurrence and progression of GC. Reverse transcription-quantitative polymerase chain reaction was used to measure miRNA-490-3p expression levels in GC tissue and adjacent healthy tissue samples. The regulatory effect of miRNA-490-3p on the proliferation and apoptosis of GC cells was detected by cell counting kit-8, colony formation assay and flow cytometry. Bioinformatic methods were used to predict AKT1 as the target of miRNA-490-3p and this was verified by a dual-luciferase reporter assay. Furthermore, western blot analysis was used to measure protein expression of AKT1 in GC cells following overexpression or knockdown of miRNA-490-3p. The present study demonstrated that miRNA-490-3p expression was downregulated in GC tissue, compared with adjacent healthy tissue. In particular, miRNA-490-3p expression levels were significantly decreased in GC tissue samples from patients with advanced cancer (stage III+IV) compared with samples from patients with early-stage (stage I+II) cancer. Additionally, miRNA-490-3p expression levels were significantly decreased in GC tissue samples from patients whose tumor size was >3 cm, compared with those <3 cm. In vitro, downregulation of miRNA-490-3p promoted cell proliferation and suppressed apoptosis. In addition, rescue experiments demonstrated that overexpression of AKT1 partially reversed the effect of miRNA-490-3p on cell proliferation and apoptosis. The present study demonstrated that miRNA-490-3p regulated proliferation and apoptosis in gastric cancer cells via direct targeting of AKT1.

Keywords: apoptosis; gastric cancer; microRNA-490-3p; proliferation; protein kinase B.