title: Transforming growth factor-β-induced lncRNA-Smad7 inhibits apoptosis of mouse breast cancer JygMC(A) cells.
abstract: Transforming growth factor (TGF)-β exhibits both pro-apoptotic and anti-apoptotic effects on epithelial cells in a context-dependent manner. The anti-apoptotic function of TGF-β is mediated by several downstream regulatory mechanisms, and has been implicated in the tumor-progressive phenotype of breast cancer cells. We conducted RNA sequencing of mouse mammary gland epithelial (NMuMG) cells and identified a long non-coding RNA, termed lncRNA-Smad7, which has anti-apoptotic functions, as a target of TGF-β. lncRNA-Smad7 was located adjacent to the mouse Smad7 gene, and its expression was induced by TGF-β in all of the mouse mammary gland epithelial cell lines and breast cancer cell lines that we evaluated. Suppression of lncRNA-Smad7 expression cancelled the anti-apoptotic function of TGF-β. In contrast, forced expression of lncRNA-Smad7 rescued apoptosis induced by a TGF-β type I receptor kinase inhibitor in the mouse breast cancer cell line JygMC(A). The anti-apoptotic effect of lncRNA-Smad7 appeared to occur independently of the transcriptional regulation by TGF-β of anti-apoptotic DEC1 and pro-apoptotic Bim proteins. Small interfering RNA for lncRNA-Smad7 did not alter the process of TGF-β-induced epithelial-mesenchymal transition, phosphorylation of Smad2 or expression of the Smad7 gene, suggesting that the contribution of this lncRNA to TGF-β functions may be restricted to apoptosis. Our findings suggest a complex mechanism for regulating the anti-apoptotic and tumor-progressive aspects of TGF-β signaling.
authors.affiliation: Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Arase
authors.forename: Kana
authors.initials: K
authors.lastname: Horiguchi
authors.forename: Shogo
authors.initials: S
authors.lastname: Ehata
authors.forename: Masato
authors.initials: M
authors.lastname: Morikawa
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Kohei
authors.initials: K
authors.lastname: Miyazono
authors.forename: Daizo
authors.initials: D
authors.lastname: Koinuma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D047468:Immunoprecipitation; D008233:Lymphotoxin-alpha / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D008233:Lymphotoxin-alpha; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D051906:Smad7 Protein; C497807:Smad7 protein, mouse
keywords: Apoptosis; Smad7; breast cancer; long non-coding RNA; transforming growth factor-β