MiR-183 inhibits autophagy and apoptosis in gastric cancer cells by targeting ultraviolet radiation resistance-associated gene

Abstract

Ultraviolet radiation resistance-associated gene (UVRAG) regulates autophagy by promoting the formation and maturation of autophagosomes. The aim of the present study was to investigate the effects of UVRAG and UVRAG-targeting miRNA on the regulation of autophagy and apoptosis in gastric cancer (GC). TargetScan was used to predict that miR-183 targets the 3′-untranslated region (UTR) of UVRAG, while the interaction between miR-183 and the 3′-UTR of UVRAG was assessed using a dual luciferase reporter assay. Autophagy was induced in the GC cell line MKN28 by serum starvation. miR-NC mimics, miR-183 mimics, miR-NC inhibitors and miR-183 inhibitors were transfected into MKN28 cells, followed by assessment of the UVRAG expression, cell viability and cell apoptosis by western blotting, reverse transcription-quantitative polymerase chain reaction, Cell Counting Kit-8 and flow cytometry, respectively. It was demonstrated that autophagy resulted in miR-183 downregulation and overexpression of UVRAG mRNA and protein in MKN28 cells. Transfection with miR-183 mimic or inhibitor affected the expression of miR-183 and, consequently, UVRAG. miR-183 overexpression reversed the starvation-induced inhibition of cell proliferation, while inhibition of miR-183 reduced the proliferation of GC cells. miR-183 overexpression reversed starvation-induced apoptosis, while miR-183 inhibition promoted starvation-induced apoptosis in GC cells. Finally, miR-183 overexpression attenuated starvation-induced autophagy (LC-3), apoptosis (Bax/Bcl-2) and UVRAG expression, while miR-183 inhibition exerted the opposite effects. In conclusion, the results of the present study indicated that miR-183 inhibits starvation-induced autophagy and apoptosis by targeting UVRAG in human GC cells.