title: MicroRNA-548j functions as a metastasis promoter in human breast cancer by targeting Tensin1.
abstract: MicroRNAs (miRNAs) are single-stranded, small non-coding RNA molecules that participate in important biological processes. Although the functions of many miRNAs in breast cancer metastasis have been established, the role of others remains to be characterized. To identify additional miRNAs involved in metastasis, we performed a genetic screen by transducing a Lenti-miR™ virus library into MCF-7 cells. Using transwell invasion assays we identified human miR-548j as an invasion-inducing miRNA. The endogenous levels of miR-548j expression in breast cancer cell lines were shown to correlate with invasiveness. Moreover, miR-548j was shown to stimulate breast cancer cell invasion and metastasis in vitro and in vivo, but had no effect on proliferation. Next, using a series of in vitro and in vivo experiments, we found that Tensin1 served as a direct and functional target of miR-548j. Both miR-548j and Tensin1 modulated the activation of Cdc42 to regulate cell invasion and siCdc42 or the selective Cdc42 inhibitor ML141 suppressed the pathway of miR-548j-mediated cell invasion. Furthermore, a strong correlation between miR-548j, Tensin1, metastasis and survival was observed using two sets of clinical breast cancer samples. Our findings demonstrate that miR-548j functions as a metastasis-promoting miRNA to regulate breast cancer cell invasion and metastasis by targeting Tensin1 and activating Cdc42, suggesting a potential therapeutic application in breast cancer.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Collaborative Innovation Center for Cancer Medicine, Beijing 100021, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
authors.forename: Xiaoshuan
authors.initials: X
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Collaborative Innovation Center for Cancer Medicine, Beijing 100021, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Baona
authors.initials: B
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Collaborative Innovation Center for Cancer Medicine, Beijing 100021, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Collaborative Innovation Center for Cancer Medicine, Beijing 100021, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Collaborative Innovation Center for Cancer Medicine, Beijing 100021, China.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Collaborative Innovation Center for Cancer Medicine, Beijing 100021, China. Electronic address: liuzh@cicams.ac.cn.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D000070876:Tensins / Q000235:genetics*
chemical_list: C561887:MIRN548 microRNA, human; D035683:MicroRNAs; C000603369:TNS1 protein, human; D000070876:Tensins
keywords: Breast cancer; Cdc42; Metastasis; Tensin1; miR-548j