Abstract
Retinoblastoma (RB) is the most common malignancy in children. Due to refractory mechanisms of chemoresistance and the toxicity of chemotherapies, novel therapies for RB treatment are urgently required. MicroRNA-320 (miR-320) is believed to be associated with the tumorigenesis of RB, although the mechanism remains unclear. Considering the hypoxic intratumoral region, the roles of miR-320 and hypoxia inducible factor-1α (HIF-1α) in the regulation of autophagy were investigated in 30 human RB samples and WERI-RB1 cells. The results demonstrated that HIF-1α was the downstream target of miR-320, and decreased miRNA-320 or HIF-1α lead to the inhibition of autophagy in WERI-RB1 cells. Compared with WERI-RB1 cells that were not transfected, silenced HIF-1α caused a 1.41-fold increase (P<0.01) in p62, a 2.71-fold decrease of Beclin1, and inhibited miRNA-320. Silenced HIF-1α also resulted in 7.29- and 7.43-fold increases in phosphorylated-mechanistic target of rapamycin (mTOR) and mTOR, respectively. In conclusion, the present results suggest that miRNA-320 may regulate the development of autophagy by targeting HIF-1α and autophagy-related proteins in RB under hypoxic conditions.