title: LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis.
abstract: LncRNAs have critical roles in various biological processes ranging from embryonic development to human diseases, including cancer progression, although their detailed mechanistic functions remain illusive. The lncRNA linc-ROR has been shown to contribute to the maintenance of induced pluripotent stem cells and embryonic stem cells. In this study, we discovered that linc-ROR was upregulated in breast tumor samples, and ectopic overexpression of linc-ROR in immortalized human mammary epithelial cells induced an epithelial-to-mesenchymal transition (EMT) program. Moreover, we showed that linc-ROR enhanced breast cancer cell migration and invasion, which was accompanied by generation of stem cell properties. Contrarily, silencing of linc-ROR repressed breast tumor growth and lung metastasis in vivo. Mechanistically, our data revealed that linc-ROR was associated with miRNPs and functioned as a competing endogenous RNA to mi-205. Specifically, linc-ROR prevented the degradation of mir-205 target genes, including the EMT inducer ZEB2. Thus our results indicate that linc-ROR functions as an important regulator of EMT and can promote breast cancer progression and metastasis through regulation of miRNAs. Potentially, the findings of this study implicate the relevance of linc-ROR as a possible therapeutic target for aggressive and metastatic breast cancers.
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: P
authors.initials: P
authors.lastname: Hou
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Changchun, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: R
authors.initials: R
authors.lastname: Yao
authors.affiliation: The Breast Surgery, The Tumor Hospital of Jilin Province, Changchun, China.
authors.forename: M
authors.initials: M
authors.lastname: Ma
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Changchun, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.affiliation: The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Changchun, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Changchun, China.
authors.forename: B
authors.initials: B
authors.lastname: Huang
authors.affiliation: The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
authors.forename: J
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; C000588825:Linc-RNA-RoR, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2