LncRNA SNHG12 alleviates hypertensive vascular endothelial injury through miR-25-3p/SIRT6 pathway

Abstract

The objective of this study was to find the role of LncRNA SNHG12 in the regulation of hypertensive vascular endothelial injury. LncRNA SNHG12 and miR‐25‐3p expression were detected by quantitative RT‐PCR. Protein levels of Sirtuin 6 (SIRT6), endothelial cell (EC) senescence markers p16 and p21, and EC marker CD31 were measured by Western blot. The apoptosis of HUVECs was detected by flow cytometry. The binding between LncRNA SNHG12 and miR‐25‐3p was verified by dual luciferase reporter gene assay and RNA pull‐down assay. As a result, LncRNA SNHG12 was down‐regulated in aortic primary ECs isolated from Ang II‐induced hypertensive mice and 1 kidney/deoxycorticosterone acetate/salt‐induced hypertensive mice. In Ang II‐treated HUVECs, the expression level of SNHG12 was reduced and the overexpression of SNHG12 inhibited EC senescence markers p16 and p21 expressions, the apoptosis of HUVECs, and caspase‐3 activity. Further investigation confirmed that LncRNA SNHG12 bound to miR‐25‐3p, and negatively regulated miR‐25‐3p expression. MiR‐25‐3p directly targeted SIRT6 and negatively regulated SIRT6 expression. In addition, SNHG12 overexpression inhibited Ang II‐induced HUVECs injury through regulating miR‐25‐3p. Finally, in vivo experiments showed LncRNA SNHG12 overexpression alleviated vascular endothelial injury in Ang II‐induced hypertensive mice. In conclusion, LncRNA SNHG12 alleviates vascular endothelial injury induced by hypertension through miR‐25‐3p/SIRT6 pathway.

Vascular Endothelial Senescence: Pathobiological Insights, Emerging Long Noncoding RNA Targets, Challenges and Therapeutic Opportunities

“…The protective role of Snhg12 in the vessel wall was also revealed by a separate study ( Qian et al, 2021 ). Snhg12 expression was also reduced by Ang II in HUVECs.…”

“…Snhg12 expression was also reduced by Ang II in HUVECs. The overexpression of Snhg12 inhibited EC senescence in vitro through a miR−25−3p/SIRT6 pathway and alleviated vascular endothelial injury in Ang II−induced hypertensive mice ( Qian et al, 2021 ).…”

SIRT6 in Vascular Diseases, from Bench to Bedside

“…Some studies suggested that SIRT6 is regulated by miRNAs and lncRNAs ( e.g. , miR-25-3p, LncRNA Blnc1, and LncRNA SNHG12) in vascular cells in vitro [ 107 , 108 ]; however, the mechanisms by which SIRT6 is repressed in aging and aging-related vascular diseases remain unclear. Further studies of the detailed mechanism underlying the aging-mediated decline in SIRT6 expression and activity will improve the understanding of SIRT6 and promote the design of SIRT6-targeted therapeutic translational strategies.…”

Role of Long Noncoding RNAs in the Regulation of Cellular Immune Response and Inflammatory Diseases

“…In angiotensin II (Ang II)-induced hypertensive mice and Ang II-induced HUVEC injury models, Qian et al [ 36 ] found that the expression of lncRNA SNHG12 was significantly downregulated. The overexpression of lncRNA SNHG12 targeted miR-25-3p to increase the expression of sirtuin (SIRT) 6.…”