Downregulation of lncRNA SNHG16 inhibits vascular smooth muscle cell proliferation and migration in cerebral atherosclerosis by targeting the miR-30c-5p/SDC2 axis

Heart Vessels. 2022 Jun;37(6):1085-1096. doi: 10.1007/s00380-022-02049-4. Epub 2022 Mar 23.

Abstract

Atherosclerosis (AS) is the basic lesion underlying the occurrence and development of cerebrovascular diseases. Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in AS. We aimed to explore the role of SNHG16 in AS and the molecular mechanism of VSMC involvement in the regulation of AS. The expression levels of SNHG16, miR-30c-5p and SDC2 were detected by qRT-PCR. CCK-8, wound healing and Transwell assays were used to assess ox-LDL-induced VSMC proliferation, migration, and invasion, respectively. Western blot analysis was used to detect SDC2 and MEK/ERK pathway-related protein levels. A dual-luciferase reporter assay confirmed the binding of SNHG16 with miR-30c-5p and miR-30c-5p with SDC2. SNHG16 and SDC2 expression was upregulated in patients with AS and ox-LDL-induced VSMCs, while miR-30c-5p was downregulated. Ox-LDL-induced VSMC proliferation and migration were increased, and the MEK/ERK signalling pathway was activated. MiR-30c-5p was targeted to SNHG16 and SDC2. Downregulating SNHG16 or upregulating miR-30c-5p inhibited ox-LDL-induced VSMC proliferation and migration and inhibited MEK/ERK signalling pathway activation. In contrast, downregulating miR-30c-5p or upregulating SDC2 reversed the effects of downregulating SNHG16 or upregulating miR-30c-5p. Furthermore, downregulating SDC2 inhibited ox-LDL-induced proliferation and migration of VSMCs and inhibited activation of the MEK/ERK signalling pathway, while upregulating lncRNA SNHG16 reversed the effects of downregulating SDC2. Downregulation of SNHG16 inhibited VSMC proliferation and migration in AS by targeting the miR-30c-5p/SDC2 axis. This study provides a possible therapeutic approach to AS.

Keywords: Atherosclerosis; Cell proliferation; LncRNA SNHG16; MiR-30c-5p; Migration; SDC2.

MeSH terms

  • Atherosclerosis* / pathology
  • Cell Movement
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Down-Regulation
  • Humans
  • Intracranial Arteriosclerosis* / metabolism
  • Intracranial Arteriosclerosis* / pathology
  • Lipoproteins, LDL
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinase Kinases / pharmacology
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / metabolism
  • RNA, Long Noncoding / genetics*
  • Syndecan-2 / genetics
  • Syndecan-2 / metabolism
  • Syndecan-2 / pharmacology

Substances

  • Lipoproteins, LDL
  • MicroRNAs
  • RNA, Long Noncoding
  • SDC2 protein, human
  • SNHG16 lncRNA, human
  • Syndecan-2
  • Mitogen-Activated Protein Kinase Kinases