EBV–encoded miRNAs can sensitize nasopharyngeal carcinoma to chemotherapeutic drugs by targeting BRCA1

摘要: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy. The high expression of BART-miRNAs (miR-BARTs) during latent EBV infection in NPC strongly supports their pathological importance cancer progression. Recently, we found that several work co-operatively to modulate the DNA damage response (DDR) by reducing Ataxia-telangiectasia-mutated (ATM) activity. In this study, further investigated role miR-BARTs on DDR. immunohistochemical study showed repair gene, BRCA1, consistently down-regulated primary NPCs. Using computer prediction programs and a series reporter assays, subsequently identified negative regulatory BART2-3p, BART12, BART17-5p BART19-3p BRCA1 expression. ectopic these four suppressed endogenous EBV-negative cell lines, whereas was enhanced repressing activities C666-1 cells. More importantly, suppressing nasopharyngeal lines using miR-BART17-5p miR-BART19-3p mimics reduced capability increased sensitivity DNA-damaging chemotherapeutic drugs, cisplatin doxorubicin. Our findings suggest play novel DDR may facilitate development effective therapies.