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

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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.

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Abbreviations

AS:

Atherosclerosis

SDC2:

Syndecan2

VSMCs:

Vascular smooth muscle cells

LncRNAs:

Long noncoding RNAs

SNHG16:

LncRNA small nucleolus RNA host gene 16

CeRNAs:

Competing endogenous RNA

CCK-8:

Cell Counting Kit 8

MiRNAs:

MicroRNAs

3' UTR:

3 'Untranslated region

CTA:

CT angiography

sh-SNHG16:

Short hairpin targeting lncRNA SNHG16

ox-LDL:

Oxidized low density lipoprotein

WT:

Wild-type

MUT:

Mutant

qRT-PCR:

Quantitative real-time PCR

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Authors and Affiliations

  1. The Departement of Geriatrics, The Third Hospital of Changsha, No. 176 West Labor Road, Changsha, 410000, Hunan Province, China

    Sheng-Nan Yang, Li-Ying Zhong, Ye-Hai Sun, Cong Wang, Wen-Juan Ru, Run-Zhi Liu, Wei Dai & Shun-Dong Li

  2. Division of Cardiology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China

    Xiu-Mei Xie

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  1. Sheng-Nan Yang
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The ethics committee of the Third Hospital of Changsha approved this study. All the patients had been informed before the research, and written informed consents were obtained from them.

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Yang, SN., Zhong, LY., Sun, YH. et al. 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 37, 1085–1096 (2022). https://doi.org/10.1007/s00380-022-02049-4

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