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 miR­874 in MDR were investigated in GC. The overexpression of miR­874 reversed cancer cell drug resistance in vitro. According to reporter gene and western blot assays, Autophagy­related 16­like 1 (ATG16 L1) was identified as a direct target of miR­874. 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 miR­874/ATG16L1/autophagy regulatory loop was demonstrated to serve an important role in MDR in GC. Furthermore, miR­874 may be used as a prognostic factor in GC. Overall, miR­874 could inhibit autophagy and sensitize GC cells to chemotherapy via the target gene ATG16L1, highlighting the potential clinical application of miR­874 in chemotherapeutic resistance.