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.

The concomitant apoptosis and EMT underlie the fundamental functions of TGF-β

“…In addition, MSK1 [74], Dlx2 [75], and lncRNA-Smad7 [76] have also been shown to have effects on anti-TGF-β-induced apoptosis but their expression levels are also elevated during TGF-β-induced apoptosis and EMT. Thus, it can be concluded that the level of anti-apoptotic molecules determines the proportion of cells to survive or to undergo EMT in response to TGF-β stimulation.…”

Gastric Adenocarcinoma Predictive Long Intergenic Non-Coding RNA Promotes Tumor Occurrence and Progression in Non-Small Cell Lung Cancer via Regulation of the miR-661/eEF2K Signaling Pathway

“…It has been shown that lncRNA plays an important role in multiple molecule regulation, such as transcriptional regulation, post-transcriptional regulation, and modification [8][9][10]. For example, lncRNA GAS5 is down-regulated in NSCLC tissues and cells, and negatively correlated with miR-23a, which inhibits the occurrence of NSCLC [11].…”

Clopidogrel reduces apoptosis and promotes proliferation of human vascular endothelial cells induced by palmitic acid via suppression of the long non-coding RNA HIF1A-AS1 in vitro

“…In contrast to well-studied small ncRNA, such as miRNAs, siRNAs, and piRNAs, LncRNAs are less well characterized. Nowadays, increasing number of studies shows that LncRNAs play important roles in cancer progression and metastasis as well as cellular processes, such as cell proliferation and apoptosis [16][17][18]. Therefore, identifying the relationship between LncRNAs and hyperlipidemia-induced apoptosis of HUVECs may help understand the function of clopidogrel treatment in patients with CVD.…”