MiR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1

Abstract

Chemotherapy is an important treatment option for gastric cancer (GC); however, chemotherapy usually fails due to drug resistance, particularly multidrug resistance (MDR). In our previous studies, microRNA (miR)-874 was demonstrated to serve an important role in tumour growth, apoptosis and angiogenesis. In the present study, the precise roles and underlying mechanisms of miR-874 in MDR were investigated in GC. The overexpression of miR-874 reversed cancer cell drug resistance in vitro. According to reporter gene and western blot assays, Autophagy.related 16.like 1 (ATG16 L1) was identified as a direct target of miR-874. ATG16L1 was also demonstrated to be positively associated with autophagy. Reducing the expression of ATG16L1 and inhibiting the occurrence of autophagy sensitized GC cells to chemotherapy. Thus, the miR-874/ATG16L1/autophagy regulatory loop was demonstrated to serve an important role in MDR in GC. Furthermore, miR-874 may be used as a prognostic factor in GC. Overall, miR-874 could inhibit autophagy and sensitize GC cells to chemotherapy via the target gene ATG16L1, highlighting the potential clinical application of miR-874 in chemotherapeutic resistance.