MiR-193a-5p and -3p Play a Distinct Role in Gastric Cancer: miR-193a-3p Suppresses Gastric Cancer Cell Growth by Targeting ETS1 and CCND1

Background/Aim: MicroRNAs (miRNAs) are small non-protein-coding RNAs, that can be generated from the 5p or 3p arm of precursor miRNA (pre-miRNA). Differential miRNA arm selection has been reported between tumor and normal tissue in many cancer types; however, the biological function and mechanism of miRNA arm switching in gastric cancer remain unclear. Materials and Methods: Profiles of miRNA expression in gastric cancer were obtained from The Cancer Genome Atlas (TCGA). The biological role of miR-193a-5p/-3p in tumor growth and invasive abilities was assessed through a gain-of-function approach. Target genes of miR-193a-3p were identified using bioinformatics and an experimental approach. Results: The expression levels of miR-193a-5p, and not of miR-193a-3p, were significantly decreased in gastric cancer compared to adjacent normal tissues. Ectopic expressions of miR-193a-5p and miR-193a-3p revealed that they both inhibited gastric cancer cell growth, but only miR-193a-3p significantly suppressed cell invasion ability. Using a bioinformatics approach, we identified 18 putative target genes of miR-193a-3p. Both mRNA and protein levels of cyclin D1 (CCND1) and ETS proto-oncogene 1 (ETS1) were significantly decreased in AGS cells transfected with miR-193a-3p mimics. ETS1 or CCND1 knockdown significantly suppressed gastric cancer cell growth, similar to miR-193a-3p overexpression. Conclusion: Our results indicated that miR-193a-3p suppressed gastric growth and motility, at least partly, by directly targeting CCND1 and ETS1 expression.

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