Long noncoding RNA SNHG12 promotesvascular smooth muscle cellproliferation and migration via regulating miR-199a-5p/HIF-1α.

Abstract

The dysregulation of proliferation and migration of vascular smooth muscle cells (VSMCs) contributes to atherosclerosis (AS) and accumulating reports indicate the crucial roleof long noncoding RNA in AS. However, the roleof small nucleolar RNA host gene 12 (SNHG12) in regulating the phenotypes of VSMCs and AS remains largely unknown. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of SNHG12 and miR-199a-5p in anin vivo AS model and VSMCs treated by oxidized low-density lipoprotein (ox-LDL). The proliferation ability, migration ability, and apoptosis of VSMCs were tested by cell counting kit-8, Transwell assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay, respectively. StarBase database was used to predict the binding sites between miR-199a-5p and SNHG12. The interaction between miR-199a-5p and SNHG12 was validated by qRT-PCR, western blot, and luciferase reporter assay. Western blot was used to examine the effects of SNHG12 and miR-199a-5p on the expression of hypoxia-inducible factor 1α (HIF-1α). We found that the expression level of SNHG12 was significantly increased in the animal model and VSMCs treated by ox-LDL. Knockdown of SNHG12 suppressed the proliferation and migration abilitiesof VSMCs, while overexpression of SNHG12 had the opposite effects. Mechanically, we validated that miR-199a-5p was a target of SNHG12, and the target gene of miR-199a-5p, HIF-1α could be indirectly and positively regulated by SNHG12. In conclusion, SHNG12 targeting miR-199a-5p/HIF-1α contributed to the pathophysiological process of AS by regulating the phenotypes of VSMCs, and could be a potential therapy target for this disease.