The regulatory and predictive functions of miR-17 and miR-92 families on cisplatin resistance of non-small cell lung cancer

Jian Zhao, Wenfan Fu, Hongying Liao, Lu Dai, Zeyong Jiang, Youguang Pan, Haoda Huang, Yijun Mo, Siwen Li, Guangping Yang, Jun Yin

Chemotherapy is an important therapeutic approach for non-small cell lung cancer (NSCLC). However, a successful long-term treatment can be prevented by the occurring of chemotherapy resistance frequently, and the molecular mechanisms of chemotherapy resistance in NSCLC remain unclear. In this study, abnormal expressions of miR-17 and miR-92 families are observed in cisplatin-resistant cells, suggesting that miR-17 and miR-92 families are involved in the regulation of cisplatin resistance in NSCLC. miRNA microarray shows that miR-17 and miR-92 families are all down-regulated in cisplatin-resistant A549/DDP cells compared with cisplatin-sensitive A549 cells. The aim of this study is to investigate the regulatory functions of miR-17 and miR-92 families on the formation of cisplatin resistance and the predictive functions of them as biomarkers of platinum-based chemotherapy resistance in NSCLC. The low expressions of miR-17 and miR-92 families can maintain cisplatin resistance through the regulation of CDKN1A and RAD21. As a result of high expressions of CDKN1A and RAD21, the inhibition of DNA synthesis and the repair of DNA damage are achieved and these may be two major contributing factors to cisplatin resistance. Moreover, we demonstrate that the expressions of miR-17 and miR-92 families in NSCLC tissues are significantly associated with platinum-based chemotherapy response. Our study indicates that miR-17 and miR-92 families play important roles in cisplatin resistance and can be used as potential biomarkers for better predicting the clinical response to platinum-based chemotherapy in NSCLC.