MiR-32 induces radio-resistance by targeting DOC-2 / DAB 2 interactive protein and regulating autophagy in gastric carcinoma

The aberrant expressions of microRNAs have been proved in many solid tumors. MAiR-32 is an oncomiR in gastric cancer (GC); however, the mechanism by which miR-32 functions as a regulator of radiotherapy response and resistance in GC patient is completely uncovered. In the present study, we revealed that DOC-2/DAB2 interactive protein (DAB2IP), the miR-32-dependent tumor-suppressor gene, was down-regulated and induced autophagy, as well as inhibited radiotherapy-induced apoptosis in GC cells. miR-32 expression was up-regulated in GC, and miR-32 inhibited DAB2IP expression through a direct binding site within the DAB2IP 3’ un-translated region. MiR-32 mimics enhanced survival and decreased radio-sensitivity, which were reversed by miR-32 inhibitor. Flow cytometric analysis revealed that over-expressed miR-32, consistent with the DAB2IP-knockdown results, reduced ionizing radiation (IR)-induced cell apoptosis, which was restored by 4 nM brefeldin A treatment. More significantly, the over-expression of miR-32 and the knock-down of DAB2IP enhanced autophagy in the IR-treated GC cells. MiR-32 regulated the expression of autophagy-related proteins, such as DAB2IP, Beclin 1 and Light chain 3β I/II, phosphorylation of S6 kinase, as well as mammalian target of rapamycin (mTOR). In conclusion, these data provide novel insights into the mechanisms governing the regulation of DAB2IP expression by miR-32 and their possible contribution to autophagy and radio-resistance in GC.