Long non-coding RNA XIST promotes proliferation, autophagy and inhibits apoptosis by regulating microRNA-30c/ATG5 axis in gastric cancer

Background: Gastric cancer (GC) is a great threat to human health and life. Long non-coding RNA X inactive-specific transcript (XIST) and microRNA-30c (miR-30c) function as crucial players in the tumorigenesis of GC. Bioinformatics analysis suggests that miR-30c has a chance to interact with XIST and autophagy related 5 (ATG5). Moreover, ATG5 has been identified as a target of miR-30c in human intestinal epithelial cells. Hence, whether XIST could regulate cell proliferation, apoptosis and autophagy by miR-30c/ATG5 axis was further investigated in GC. Methods: The levels of XIST, miR-30c and ATG5 mRNA were measured by RT-qPCR assay. ATG5, p62, LC3-I, and LC3-II protein expression was detected by western blot assay. The relationships of XIST, miR-30c and ATG5 were examined by luciferase, RNA immunoprecipitation (RIP) and RNA pull down assays. Cell proliferation was assessed by MTS assay. Cell apoptotic rate was determined using flow cytometry. ATG5 protein expression in tissues was measured by immunohistochemistry (IHC) assay. Results: XIST was highly expressed in GC tissues and cell lines. XIST knockdown suppressed proliferation, autophagy and promoted apoptosis in GC cells. XIST inhibited miR-30c expression by direct interaction in GC cells. Furthermore, miR-30c depletion abrogated XIST deficiency-mediated anti-proliferation, pro-apoptosis and anti-autophagy effects in GC cells. Additionally, ATG5 was a target of miR-30c and XIST promoted ATG5 expression by sequestering miR30c from ATG5 in GC cells. Conclusion: XIST knockdown suppressed proliferation, autophagy and induced apoptosis through regulating miR-30c/ATG5 axis in GC cells, hinting at the potential value of XIST in the management of GC.