miR-7 modulates chemoresistance of small cell lung cancer by repressing MRP1/ABCC1.

MicroRNAs (miRNAs) represent a class of small non-coding RNAs and have been shown to play important roles in various biological processes including cell growth, differentiation and apoptosis by regulating the target genes. miR-7 has been described not only as a tumour suppressor gene but also as an oncogene in human cancers. The aim of this study was to investigate the functional roles of miR-7 in chemoresistance of SCLC and its underlying mechanism. By using a bioinformatic assay, we found that MRP1/ABCC1 was a potential target gene of miR-7. Expression of miR-7 and MRP1/ABCC1 was examined in 44 SCLC samples by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry methods. Low-level expression of miR-7 was associated significantly with drug responsiveness and overall survival rate of patients with SCLC, but not with gender, age and stage. There was an inverse relationship between miR-7 and MRP1/ABCC1 expression. Downregulation of MRP1/ABCC1 level was revealed after transfection with a miR-7 mimic in H69 AR cells. Transfection of a miR-7 inhibitor into H69 cells restored MRP1/ABCC1 expression. A dual-luciferase reporter assay confirmed that miR-7 targeted predicted sites in the 3'-untranslated region (3'-UTR) of the MRP1/ABCC1 gene. Our data suggested that miR-7 mediated SCLC chemoresistance by repressing MRP1/ABCC1 and may be a prognostic predictor and potential therapeutic target in human SCLC.