Conclusions
SENCR alleviates TGF-β-induced EndMT and sponges miR-126a expression via direct inhibition of the negative regulator of TGF-β/Smad signaling SMURF2.
Material and methods
Human carotid plaque samples and human coronary endothelial cells (HACECs) were collected to examine the expression of SENCR. Quantitative PCR and immunoblots were performed to evaluate the expression of SENCR and miR-126a in HACECs in response to TGF-β1 and transfected with small interfering RNA.
Methods
Human carotid plaque samples and human coronary endothelial cells (HACECs) were collected to examine the expression of SENCR. Quantitative PCR and immunoblots were performed to evaluate the expression of SENCR and miR-126a in HACECs in response to TGF-β1 and transfected with small interfering RNA.
Results
We found that SENCR was significantly decreased in carotid plaques as compared to normal carotids. Knockdown of SENCR in HACECs aggravated the expression of smooth muscle markers α-SMA and calponin induced by TGF-β1 but repressed the expression of endothelial markers platelet/endothelial cell adhesion molecule 1 (PECAM1) and VE-cadherin down-regulated by TGF-β1. Through bioinformatic analysis and Luciferase assay, miR-126a was identified as the direct target of SENCR. Further mechanistic experiments revealed that overexpression of miR-126a bound to the 3'UTR region of SMURF2 and inhibited the expression of SMURF2, which was considered as the negative regulator of TGF-β/Smad signaling. Finally, overexpression of miR-126a did not restore the decreased expression of the smooth muscle markers α-SMA and calponin under the condition of SMURF2 depletion, suggesting that the effect of miR-126a on EndMT progression is SMURF2 dependent. Conclusions: SENCR alleviates TGF-β-induced EndMT and sponges miR-126a expression via direct inhibition of the negative regulator of TGF-β/Smad signaling SMURF2.