Long noncoding RNA SNHG12 promotes vascular smooth muscle cell proliferation 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 role of long noncoding RNA in AS. However, the role of 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 an in 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 abilities of 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.

MicroRNA‐199a‐5p aggravates angiotensin II–induced vascular smooth muscle cell senescence by targeting Sirtuin‐1 in abdominal aortic aneurysm

“…Second, whether miR‐199a‐5p contributes to AAA formation via regulation of VSMC senescence needs to be further verified in Ang II–infused Apoe ‐/‐ mice. Third, it has been reported that SHNG12 targeting miR‐199a‐5p/HIF‐1α contributed to atherosclerosis formation by mediating the phenotypes of VSMCs 42 . In addition to Sirt1, whether miR‐199a‐5p mediates VSMC senescence via regulation of other targets needs to be addressed in future study.…”

“…Third, it has been reported that SHNG12 targeting miR‐199a‐5p/HIF‐1α contributed to atherosclerosis formation by mediating the phenotypes of VSMCs. 42 In addition to Sirt1, whether miR‐199a‐5p mediates VSMC senescence via regulation of other targets needs to be addressed in future study. Fourth, whether miR‐199a‐5p can injure other cell types including endothelial cells and fibroblasts to promote AAA formation has not been demonstrated.…”

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

“…These data further confirmed the beneficial role of SNHG12 in the hypertensive vascular endothelial injury by targeting miR‐25‐3p. In addition, the research of Sun et al 43 . showed that SNHG12 was increased in oxidized low‐density lipoprotein‐treated vascular smooth muscle cells (VSMCs) and promoted the proliferation and migration of VSMCs, indicating SNHG12 is also involved in the atherosclerosis progression.…”

Expression Profile Analysis to Identify Circular RNA Expression Signatures in Muscle Development of Wu'an Goat Longissimus Dorsi Tissues

“…Among them, miR-199a-5p might play a key role in muscle aging. In addition, some researchers have observed that the overexpression of miR-199a-5p can inhibit the proliferation and migration of vascular smooth muscle cells, which can also suppress their apoptosis ( 36 ). Compared with traditional small-tailed Han sheep, Qianhua Mutton Merino is a new breed of sheep for which meat performance has been improved.…”