Autophagy-regulating microRNAs: potential targets for improving radiotherapy.

Abstract

Radiotherapy (RT) is one of the most important therapeutic strategies against cancer. However, resistance of cancer cells to radiation remains a major challenge for RT. Thus, novel strategies to overcome cancer cell radioresistance are urgent. Macroautophagy (hereafter referred to as autophagy) is a biological process by which damaged cell components can be removed and accordingly represent a cytoprotective mechanism. Because radiation-induced autophagy is associated with either cell death or radioresistance of cancer cells, a deeper understanding of the autophagy mechanism triggered by radiation will expedite a development of strategies improving the efficacy of RT. MicroRNAs (miRNAs) are involved in many biological processes. Mounting evidence indicates that many miRNAs are involved in regulation of the autophagic process induced by radiation insult, but the underlying mechanisms remain obscure. Therefore, a deep understanding of the mechanisms of miRNAs in regulating autophagy and radioresistance will provide a new perspective for RT against cancer. We summarized the recent pertinent literature from various electronic databases, including PubMed. We reviewed the radiation-induced autophagy response and its association of the role, function and regulation of miRNAs, and discussed the feasibility of targeting autophagy-related miRNAs to improve the efficacy of RT. The beneficial or harmful effect of autophagy may depend on the types of cancer and stress. The cytoprotective role of autophagy plays a dominant role in cancer RT. For most tumor cells, reducing radiation-induced autophagy can improve the efficacy of RT. MiRNAs have been confirmed to take part in the autophagy regulatory network of cancer RT, the autophagy-regulating miRNAs therefore could be developed as potential targets for improving RT.