title: MiR-106b expression determines the proliferation paradox of TGF-β in breast cancer cells.
abstract: TGF-β has paradoxical effects on cancer cell proliferation, as it suppresses proliferation of normal epithelial and low-invasive cancer cells, but enhances that of high-invasive cancer cells. However, how cancer cells acquire the ability to evade the tumor-suppressing effects of TGF-β, yet still take advantage of its tumor-promoting effects, remains elusive. Here, we identified miR-106b as a molecular switch to determine TGF-β effects on cell proliferation. TGF-β1 enhances the transcription of miR-106b via a promoter independent of its host gene MCM7 by activating c-jun. In high-invasive breast cancer cells, miR-106b is upregulated by TGF-β1 at a much higher level than that in normal or low-invasive cancer cells. Accumulation of miR-106b counterbalances TGF-β growth-inhibiting effects by eliminating activated retinoblastoma (RB) and results in enhanced proliferation. Furthermore, miR-106b mediates TGF-β effects on tumor growth and metastasis in breast cancer xenografts. In addition, miR-106b expression is elevated in higher stage tumors and correlated with tumor progression in breast cancer patients. These findings suggest that high level of miR-106b induced by TGF-β determines the tumor-promoting effects of TGF-β in breast cancer.
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Gong
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Qu
authors.affiliation: 1] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China [2] Key Laboratory of Gene Engineering of Ministry, State Key Laboratory of Biocontrol, School of Life Science, Sun Yat-Sen University, Guangzhou, China.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Pan
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Nie
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Su
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China [3] Key Laboratory of Gene Engineering of Ministry, State Key Laboratory of Biocontrol, School of Life Science, Sun Yat-Sen University, Guangzhou, China.
authors.forename: E
authors.initials: E
authors.lastname: Song
mesh_terms: D000328:Adult; D000818:Animals; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C542541:MIRN106 microRNA, human; D035683:MicroRNAs; C543896:Mirn106 microRNA, mouse; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta