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LncRNA BANCR induced vascular smooth muscle cell proliferation by downregulating miR-34c methylation in atherosclerosis

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Abstract

Aberrant vascular smooth muscle cell (VSMCs) proliferation involves in the development of atherosclerosis. It reported that Long noncoding BRAF-activated noncoding RNA (BANCR) and miR-34c played opposite roles in the regulation of the proliferation of VSMCs, indicating that there might be a potential interaction between them. This study was to investigate the relationship between BANCR and miR-34c in atherosclerosis. Blood (5 ml) was obtained from 56 patients with atherosclerosis and 56 healthy volunteers after they were fasted overnight, and plasma was extracted from the blood. Human Aortic Smooth Muscle Cells (HASMCs) were used to perform in vitro cell experiments. RT-qPCR was performed to measure the expression of BANCR and miR-34c in plasma and HASMCs. Dual luciferase reporter assay detected the interaction between BANCR and miR-34c. CCK-8 assay was used to assess the effects of BANCR and miR-34c overexpression on the proliferation of HASMCs. Western blotting was used to assess the effects of BANCR and miR-34c overexpression on the protein expression of HMGB1, TNF-ɑ and Bcl-2. In this study, we found that BANCR was upregulated, while miR-34c was downregulated in atherosclerosis. Bioinformatics analysis showed that BANCR and miR-34c could directly interact with each other. Moreover, overexpression of BANCR could decrease the expression of miR-34c in HASMCs, but overexpression of miR-34c could not affect the expression of BANCR. Furthermore, overexpression of BACNR increased miR-34c methylation, and knockdown of endogenous BANCR decreased miR-34c methylation. In addition, overexpression of BANCR reduced the effects of miR-34c on HASMCs proliferation and reversed the effects of miR-34c on HMGB1, TNF-ɑ and Bcl-2 expression. BANCR overexpression could induce HASMCs proliferation by downregulating the miR-34c methylation. Therefore given BANCR upregulation in atherosclerosis, its expression may be considered as a novel and useful biomarker for atherosclerosis prevention and prognosis. However considering the possible effects of other underlying diseases on both BANCR expression and miR-34c in atherosclerosis, further investigation is suggested for future research.

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Data availability

The datasets generated and/or analyzed during the current study are not publicly available due research design, but are available from the corresponding author on reasonable request.

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  1. Xiao Jiang and Zhijun Liu have contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Cardio Cerebrovascular Disease Branch of General Hospital of Ningxia Medical University, No. 6 Ning’an East Lane, Jinfeng District, Yinchuan, Ningxia Province, 750004, China

    Xiao Jiang, Zhijun Liu & Xijuan Qi

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Contributions

XJ and ZJL: literature research, experiment studies, research design, data analysis, and manuscript writing. XJQ: data analysis, experiment work, manuscript editing and clinical studies. All authors read and approved the final manuscript.

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Correspondence to Xiao Jiang.

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General Hospital of Ningxia Medical University Ethics Committee approved this study (GHNMU2018050625532). All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Jiang, X., Liu, Z. & Qi, X. LncRNA BANCR induced vascular smooth muscle cell proliferation by downregulating miR-34c methylation in atherosclerosis. J Thromb Thrombolysis 51, 924–932 (2021). https://doi.org/10.1007/s11239-020-02314-1

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