Restoration of miR-26b expression partially reverses the cisplatin resistance of NSCLC by targeting tafazzin.

Abstract

BackgroundDysregulation of microRNAs has been reported to be responsible for drug resistance of cancers. However, the association between aberrant expression of miR-26b and cisplatin resistance in non-small cell lung cancer (NSCLC) remains unclear.MethodsPC9 and A549 were used to establish the cisplatin resistance models on NSCLC. Expression of miR-26b in cisplatin-resistant PC9 and A549 cells (PC9/R and A549/R) was detected by quantitative real-time PCR assays. Drug sensitivity and mitochondrial apoptosis were detected by Cell Counting Kit-8 assay and flow cytometry assay, respectively. The target relationship between miR-26b and tafazzin (TAZ) was validated by dual-luciferase reporter assay.ResultsObvious downregulation of miR-26b was observed in PC9/R and A549/R cells. Restoration of miR-26b partially reversed the cisplatin resistance of PC9/R and A549/R cells. Expression of TAZ was increased in PC9/R and A549/R cells compared to the parental PC9 and A549 cells. Results of dual-luciferase reporter assays verified that TAZ was targeted by miR-26b. We showed that restoration of miR-26b expression inhibited the TAZ expression and thus expanded the mitochondrial pathway of apoptosis induced by cisplatin in PC9/R and A549/R cells.ConclusionRestoration of miR-26b expression partially reverses the cisplatin resistance of NSCLC by targeting TAZ. miR-26b/TAZ axis may represent a potential strategy to reverse the cisplatin in NSCLC.