Wang S, Zhang R, Claret FX, Yang H
Nasopharyngeal carcinoma (NPC) is a malignant tumor originating in the epithelium. Radiotherapy is the standard therapy, but tumor resistance to this treatment reduces the 5-year patient survival rate dramatically. Studies are urgently needed to elucidate the mechanism of NPC radioresistance. Epigenetics - particularly microRNAs (miRNAs) and DNA methylation - plays an important role in carcinogenesis and oncotherapy. We used qRT-PCR analysis and identified a miRNA signature from differentially expressed miRNAs. Our objectives were to identify the role of miR-24 in NPC tumorigenesis and radioresistance and to identify the mechanisms by which miR-24 is regulated. We found that miR-24 inhibited NPC cell growth, promoted cell apoptosis, and suppressed the growth of NPC xenografts. We showed that miR-24 was significantly downregulated in recurrent NPC tissues. When combined with irradiation, miR-24 acted as a radiosensitizer in NPC cells. One of the miR-24 precursors was embedded in a CpG island. Aberrant DNA methylation was involved in NPC response to radiotherapy, which linked inactivation of miR-24 through hypermethylation of its precursor promoter with NPC radioresistance. Treating NPC cells with the DNA-hypomethylating agent 5-aza-2'-deoxycytidine compensated for the reduced miR-24 expression. Together, our findings showed that miR-24 was negatively regulated by hypermethylation of its precursor promoter in NPC radioresistance. Our findings defined a central role for miR-24 as a tumor-suppressive miRNA in NPC and suggested its use in novel strategies for treatment of this cancer.