title: miR-96 promotes tumor proliferation and invasion by targeting RECK in breast cancer.
abstract: microRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression in diverse biological processes. The aim of the present study was to investigate the expression pattern of miR-96 in breast cancer and its biological role in tumor progression. The expression levels of miR-96 were analyzed in 38 breast cancer specimens and 6 breast cancer cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of miR-96 on proliferation was evaluated by MTT assays, and cell migration and invasion were evaluated by transwell assays in MDA-MB-231 human breast cancer cells. Luciferase reporter assays were performed to validate the regulation of a putative target of miR-96. The effects of modulating miR-96 on endogenous levels of this potential target were subsequently confirmed via qRT-PCR and western blot analysis. We found that expression of miR-96 was commonly upregulated in breast cancer cells and breast cancer specimens when compared with that in non-malignant breast epithelial cells and adjacent normal tissues. Ectopic expression of miR-96 promoted cellular proliferation, migration and invasion of breast cancer cells, whereas inhibition of miR-96 suppressed those functions. Luciferase assays revealed that miR-96 directly bound to the 3'-untranslated region (3'-UTR) of RECK. qRT-PCR and western blot analysis confirmed that miR-96 regulated the expression of RECK both at the mRNA and protein levels. Knockdown of RECK expression in MDA-MB-231 cells by siRNA significantly promoted cell proliferation, migration and invasion. Collectively, miR-96 was significantly upregulated in breast cancer. our data also delineate the molecular pathway by which miR-96 promotes breast cancer proliferation, migration and invasion. Our findings may have important implications for the treatment of breast cancer.
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Xiangjie
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Microbiology and Genetic Institute, University of Paris 11, Paris, France.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fang
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D034622:RNA Interference
chemical_list: D020413:3' Untranslated Regions; D058851:GPI-Linked Proteins; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; C115460:RECK protein, human