MiR-23a sensitizes nasopharyngeal carcinoma to irradiation by targeting IL-8/Stat3 pathway

Abstract

Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment, but little is known about how miRNA regulates this phenomenon. In this study, we investigated the function and mechanism of miR-23a in NPC radioresistance, one of downregulated miRNAs in the radioresistant NPC cells identified by our previous microarray analysis. We observed that miR-23a was frequently downregulated in the radioresistant NPC tissues, and its decrement correlated with NPC radioresistance and poor patient survival, and was an independent predictor for reduced patient survival. In vitro radioresponse assays showed that restoration of miR-23a expression markedly increased NPC cell radiosensitivity. In a mouse model, therapeutic administration of miR-23a agomir dramatically sensitized NPC xenografts to irradiation. Mechanistically, we found that reduced miR-23a promoted NPC cell radioresistance by activating IL-8/Stat3 signaling. Moreover, the levels of IL-8 and phospho-Stat3 were increased in the radioresistance NPC tissues, and negatively associated with miR-23a level. Our data demonstrate that miR-23a is a critical determinant of NPC radioresponse and prognostic predictor for NPC patients, and its decrement enhances NPC radioresistance through activating IL-8/Stat3 signaling, highlighting the therapeutic potential of miR-23a/IL-8/Stat3 signaling axis in NPC radiosensitization.