MiR-101-3p induces vascular endothelial cell dysfunction by targeting tet methylcytosine dioxygenase 2. (28th January 2020)

• Record Type: Journal Article
• Authors: Chen, Qiaoli; Li, Xiaoye; Kong, Lingjun; Xu, Qing; Wang, Zi; Lv, Qianzhou
• Is Part Of: Acta biochimica et biophysica Sinica. Volume 52:Number 2(2020)
• Page Start: 180
• Page End: 191
• Publication Date: 2020-01-28
• Subjects: endothelial cell dysfunction -- atherosclerosis -- miR-101-3p -- ROS -- TET2; Biochemistry -- Periodicals; Biophysics -- Periodicals; 572.05
• DOI: 10.1093/abbs/gmz154
• Languages: English
• ISSNs: 1672-9145

Abstract

Abstract: Endothelial cell (EC) dysfunction represents an early key event in atherosclerosis. Recently, MicroRNAs have been demonstrated to regulate EC function. miR-101-3p has been discovered to regulate cell apoptosis and proliferation in cardiovascular diseases. Therefore, the aim of the current study was to clarify whether miR-101-3p regulates the dysfunction of vascular endothelial cells. In this study, the transfection of human umbilical vein endothelial cells (HUVECs) with miR-101-3p mimic induced reactive oxygen species (ROS) production, EC dysfunction, and activated nuclear factor-κB (NF-κB), whereas transfection with miR-101-3p inhibitor alleviated these events. The antioxidant N -acetylcysteine alleviated miR-101-3p-induced EC dysfunction. Moreover, we observed that miR-101-3p inhibited the expression of tet methylcytosine dioxygenase 2 (TET2) at the posttranscriptional level, resulting in increased ROS production and activated NF-κB. TET2 overexpression inhibited ROS production, EC dysfunction, and NF-κB activation in miR-101-3p-transfected HUVECs. These results indicate that miR-101-3p induces EC dysfunction by targeting TET2, which regulates ROS production, EC dysfunction, and NF-κB activation. Taken together, our current study reveals a novel pathway associated with EC dysfunction. The modulation of miR-101-3p and TET2 expression levels may serve as a potential target for therapeutic strategies for atherosclerosis.