Hsa-miR-4271 downregulates the expression of constitutive androstane receptor and enhances in vivo the sensitivity of non-small cell lung cancer to gefitinib.

The efficacy of molecular targeting agents is dependent on the metabolism or nuclear receptor-mediated clearance of chemotherapy resistance-related factors such as cytochrome P450 (CYP) or ATP binding cassette subfamily B member 1 (ABCB1). In this study, we revealed the roles of the microRNA-4271/CAR (constitutive androstane receptor) axis in the regulation of the resistance to molecular anticancer targeting agents in non-small cell lung cancer (NSCLC) cells including two main categories of NSCLC: lung adenocarcinoma (AC) and large cell lung cancer (LCC). The expression of miR-4271 was negatively correlated with CAR expression in NSCLC tissues. MiR-4271 targeted CAR and inhibited the activation of the CAR signaling pathway. Overexpression of CAR in NSCLC enhanced the resistance of NSCLC cells to molecular targeting agents and miR-4271-infected NSCLC cells enhanced their sensitivity to molecular targeting agents such as Gefitinib. The mechanism-data showed that overexpression of miR-4271 decelerated the mechanism or the clearance of molecular targeting agents by targeting the 3'UTR (3' un-translation region). These results suggest that miR-4271 may contribute to the development of more effective strategies for the treatment of advanced NSCLC.