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.

中文翻译：

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长非编码RNA SNHG12通过调节miR-199a-5p /HIF-1α促进血管平滑肌细胞增殖和迁移。

血管平滑肌细胞（VSMC）的增殖和迁移失调导致动脉粥样硬化（AS），并且越来越多的报道表明长非编码RNA在AS中起着至关重要的作用。但是，小核仁RNA宿主基因12（SNHG12）在调节VSMC和AS表型中的作用仍然未知。定量逆转录聚合酶链反应（qRT-PCR）用于检测体内AS模型和经氧化的低密度脂蛋白（ox-LDL）处理的VSMC中SNHG12和miR-199a-5p的表达水平。通过细胞计数试剂盒-8，Transwell测定法和末端脱氧核苷酸转移酶dUTP缺口末端标记测定法分别测试了VSMC的增殖能力，迁移能力和凋亡。使用StarBase数据库预测miR-199a-5p与SNHG12之间的结合位点。miR-199a-5p与SNHG12之间的相互作用已通过qRT-PCR，Western印迹和荧光素酶报告基因分析验证。用蛋白质印迹法检查了SNHG12和miR‐199a‐5p对缺氧诱导因子1α（HIF‐1α）表达的影响。我们发现在用ox-LDL处理的动物模型和VSMC中SNHG12的表达水平显着增加。抑制SNHG12抑制了VSMC的增殖和迁移能力，而SNHG12的过表达则相反。在机械上，我们验证了miR-199a-5p是SNHG12的靶标，并且miR-199a-5p，HIF-1α的靶基因可以被SNHG12间接和正向调控。总之，靶向miR-199a-5p /HIF-1α的SHNG12通过调节VSMC的表型促进了AS的病理生理过程，