OncoTargets and Therapy (Sep 2019)
Restoration of miR-26b expression partially reverses the cisplatin resistance of NSCLC by targeting tafazzin
Abstract
Shuzhi Zang,1 Shasha Zhao,2 Xinyuan Gao,1 Yunxia Li,3 Chunlei Zhong,3 Jianlian Gao4 1Respiratory Ward 1, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, People’s Republic of China; 2Respiratory Intensive Care Unit, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, People’s Republic of China; 3Respiratory Ward 2, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, People’s Republic of China; 4Clinical Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, People’s Republic of ChinaCorrespondence: Shuzhi ZangRespiratory Ward 1, The First Affiliated Hospital of Xinxiang Medical University, No. 88, Jiankang Road, Weihui City, Henan Province 453100, People’s Republic of ChinaEmail [email protected]: Dysregulation 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.Methods: PC9 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.Results: Obvious 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.Conclusion: Restoration 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.Keywords: NSCLC, cisplatin, resistance, miR-26b, TAZ
