title: miR-7 modulates chemoresistance of small cell lung cancer by repressing MRP1/ABCC1.
abstract: 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.
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.|Department of Pathology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou medical college, Guangzhou, China.
authors.forename: Huanxin
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pathology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou medical college, Guangzhou, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Linlang
authors.initials: L
authors.lastname: Guo
mesh_terms: D000328:Adult; D000368:Aged; D019295:Computational Biology / Q000379:methods; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C549242:MIRN7-1 microRNA, human; C421109:multidrug resistance-associated protein 1
keywords: MRP1/ABCC1; SCLC; chemoresistance; miR-7