LncRNA LINC00961 regulates endothelial‑mesenchymal transition via the PTEN‑PI3K‑AKT pathway

Abstract

The long noncoding RNA LINC00961 plays a crucial role in cancer and cardiovascular diseases. In the present study, the role and underlying mechanism of LINC00961 in endothelial-mesenchymal transition (EndMT) induced by transforming growth factor beta (TGF-β), was investigated. Human cardiac microvascular endothelial cells were transfected with LV-LINC00961 or short hairpin LINC00961 plasmids to overexpress or knock down LINC00961 in the cells, respectively. The cells were then exposed to TGF-β in serum-free medium for 48 h to induce EndMT. Flow cytometric analysis, Cell Counting Kit-8 assay and immunofluorescence staining were performed to examine the cell apoptosis rate, assess cell viability, and identify CD31 + /α-SMA + double-positive cells, respectively. Western blotting and reverse transcription- quantitative polymerase chain reaction were used to evaluate protein and mRNA expression, respectively. Injury to endothelial cells and EndMT was induced by TGF-β in a time-dependent manner. LINC00961 overexpression promoted injury and EndMT, whereas LINC00961 knockdown had the opposite effects. Knockdown of LINC00961 attenuated EndMT and injury to endothelial cells induced by TGF-β via the PTEN-PI3K-AKT pathway. Inhibition of LINC00961 expression may prevent the occurrence of EndMT-related cardiovascular diseases, such as myocardial fibrosis and heart failure. Therefore, LINC00961 shows potential as a therapeutic target for cardiovascular diseases.

Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis: Focus on the TGF-β/Smad signaling pathway

“…For example, EndMT plays an important role in pathophysiological processes such as myocardial ischemia-reperfusion, MI, diabetic cardiomyopathy, and fibrosis. There is an example: EndMT plays an important role in pathophysiological processes such as myocardial ischemia-reperfusion, myocardial infarction, diabetic cardiomyopathy, and fibrosis; and TGF-β-induced EndMT can be attenuated by knocking down the LINC00961 by a mechanism related to activation of phosphatase and tensin homolog (PTEN) expression and inhibition of PI3K, AKT, and mammalian target of rapamycin (mTOR) ( Hu et al, 2022 ). mTOR, as a PI3K- Akt downstream gene, mainly regulates the cardiac fibrosis by affecting the expressions of pro-fibrotic factors.…”

Preliminary investigation on the effect of extracorporeal shock wave combined with traction on joint contracture based on PTEN‐PI3K/AKT pathway

“…Phosphatase and tensin homolog (PTEN) plays an important role in regulating embryonic development and cell growth, differentiation, apoptosis, and migration, and it mainly exerts biological functions by controlling cell signal transduction pathways. PTEN has phosphatase activity and can regulate downstream pathways through phosphorylation and dephosphorylation 7,8 . PI3K/Akt signaling pathway receives inhibitory regulation by PTEN, an important signaling pathway that regulates cell growth, proliferation, survival, and apoptosis, and it regulates glycogen synthesis and glucose conversion, which are closely associated with reduced cell proliferation and apoptosis 9,10 .…”

“…PTEN has phosphatase activity and can regulate downstream pathways through phosphorylation and dephosphorylation. 7,8 PI3K/Akt signaling pathway receives inhibitory regulation by PTEN, an important signaling pathway that regulates cell growth, proliferation, survival, and apoptosis, and it regulates glycogen synthesis and glucose conversion, which are closely associated with reduced cell proliferation and apoptosis. 9,10 Zhuang et al 11 established a rat knee fibrosis model by knee immobilization, and found that the decreased PTEN gene expression in fibroblasts in fibrotic joints, followed by decreased PTEN protein translation expression, activated PI3K/AKT signaling pathway, which promoted myofibroblast proliferation and facilitated the development of joint fibrosis.…”