Radioresistance remains a challenge during nasopharyngeal carcinoma (NPC) radiotherapy. Numerous studies suggest that the miRNAs may play important roles in the regulation of radioresistance. miRNA-17-5p, which is located within the miR-17-92a cluster, could modulate tumor progression in different tissues by targeting multiple tumor associated genes. However, whether it is correlated with the radioresistance of tumor cells has not yet been elucidated. In our study, we have observed increasing miR-17-5p expression in radioresistant NPC tissues. The functional experiments suggested that miR-17-5p could clearly promote NPC cell proliferation and the cell cycle even after X-ray irradiation. Irradiation leads to tumor cell damage and death via ROS generation. The overexpression of miR-17-5p could protect NPC cells from apoptosis induced by irradiation. In addition, an in vivo experiment indicated that miR-17-5p promoted tumor growth with radiotherapy using the xenograft tumor model. A bioinformatics analysis and reporter assay were carried out to demonstrate that PTEN, which is a key regulator of AKT phosphorylation, is a target of miR-17-5p. The overexpression of miR-17-5p directly suppresses the mRNA and protein expression of PTEN. In addition, the rescue experiments showed that the AKT inhibitor can diminish the proliferation, promotion, and apoptosis inhibition effects on radioresistant NPC cells mediated by miR-17-5p. In conclusion, our findings demonstrated that miR-17-5p can enhance the radioresistance of NPC through the PTEN/AKT pathway, which is a biomarker of radioresistant NPC and a potential target for new therapeutic strategies.
Keywords: AKT; Nasopharyngeal carcinoma; PTEN; ROS; miR-17-5p; radioresistance.
IJCEP Copyright © 2019.