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

Summary 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.
Source: International Journal of Experimental Pathology - Category: Pathology Authors: Tags: Original Article Source Type: research