MicroRNA-143 enhances chemosensitivity of Quercetin through autophagy inhibition via target GABARAPL1 in gastric cancer cells

MicroRNAs have emerged as fundamental regulators in gene expression through silencing gene expression at the post-transcriptional and translational levels. In this study, miR-143 expression and biological functions in AGS/MNK28 cell lines was investigated. Results indicated that the expression of miR-143 was significantly down-regulated in cancer tissues and in gastric cancer (GC) cell lines. Target prediction algorithms (Target Scan and miRanda) showed that GABARAPL1 was a potential target gene of miR-143. GABARAPL1, also regarded as autophagy-related protein 8 (Atg8) is a ubiquitin-like protein required for the formation of autophagosomal membranes. Then, several different assays were conducted to detect autophagy in AGS/MNK28 after transfected with miR-143. In the present study, miR-143 was firstly identified as a autophagy inhibitor in GC cells via targeting GABARAPL1. Quercetin is one of the most prominent dietary antioxidants in human diet and lately it is grabbing some serious attention as a potentially powerful cancer fighter. However, the effect of Quercetin was unexpected decreased in GC cells on account of the appearance of Quercetin-induced autophagy. Therefore, applicable autophagy inhibitors might enhance the chemosensitivity of Quercetin. Furthermore, the therapeutic response of Quercetin in the combination of miR-143 was evaluated by MTT, Hochest and western blot, results suggesting that the chemosensitivity of Quercetin was enhanced when in combination with miR-143 in AGS/MNK28 cells. In conclusion, we determined miR-143 as a potent inhibitor of autophagy via targeting GABARAPL1 and miR-143 could improve the efficacy of Quercetin though autophagy inhibition in GC cell lines, thus representing a novel potential therapeutic target for gastric cancer. (C) 2015 Elsevier Masson SAS. All rights reserved.