Transforming growth factor‐β‐induced lnc RNA ‐Smad7 inhibits apoptosis of mouse breast cancer Jyg MC (A) cells

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 ( NM u MG ) cells and identified a long non‐coding RNA , termed lnc RNA ‐Smad7, which has anti‐apoptotic functions, as a target of TGF ‐β. lnc RNA ‐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 lnc RNA ‐Smad7 expression cancelled the anti‐apoptotic function of TGF ‐β. In contrast, forced expression of lnc RNA ‐Smad7 rescued apoptosis induced by a TGF ‐β type I receptor kinase inhibitor in the mouse breast cancer cell line Jyg MC (A). The anti‐apoptotic effect of lnc RNA ‐Smad7 appeared to occur independently of the transcriptional regulation by TGF ‐β of anti‐apoptotic DEC 1 and pro‐apoptotic Bim proteins. Small interfering RNA for lnc RNA ‐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 lnc RNA 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.