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Circular RNA circ_0124644 exacerbates the ox-LDL-induced endothelial injury in human vascular endothelial cells through regulating PAPP-A by acting as a sponge of miR-149-5p

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Abstract

The modulatory roles of numerous circular RNAs (circRNAs) have been exposited in atherosclerosis (AS). Our study paid attention to the function of circRNA_ 0124644 (circ_0124644) in AS development, as well as its functional mechanism. The AS cell model was established by the treatment of oxidized low-density lipoprotein (ox-LDL) to human vascular endothelial cells (HUVECs). Cell proliferation and cycle were severally measured by Cell Counting Kit-8 (CCK-8) and cell cycle detection kit. The examination of apoptosis rate was executed through flow cytometry. Western blot was exploited for detecting the associated proteins. The expression levels of circ_0124644 and microRNA-149-5p (miR-149-5p) and pregnancy-associated plasma protein-A (PAPP-A) were assayed using quantitative real-time polymerase chain reaction. The combination of targets was validated via the dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull-down assay. Clonal capacity was analyzed using colony formation assay. Ox-LDL restrained HUVECs proliferation and cycle, but facilitated apoptosis. Circ_0124644 expression was increased, while miR-149-5p was downregulated in ox-LDL-treated HUVECs. Besides, circ_0124644 served as a molecular sponge of miR-149-5p and intensified the ox-LDL-induced HUVECs injury by sponging miR-149-5p. PAPP-A was a target of miR-149-5p and miR-149-5p could mitigate the HUVECs injury caused by ox-LDL through inhibiting PAPP-A. Moreover, PAPP-A was positively regulated by circ_0124644 via the miR-149-5p. In this report, we concluded the promoted role of circ_0124644 in the ox-LDL-induced endothelial injury of HUVECs via the miR-149-5p/PAPP-A axis with an emphasis on its diagnostic and therapeutic values in AS.

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Authors and Affiliations

  1. Department of Ulcers and Vascular Surgery, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Gang Wang, Zhenbin Liu, Menghu Li, Qingwei Lu, Yanfang Li, Zengzhen Lu, Li Niu, Zixuan Fan & Zhangcheng Lei

  2. Department of Pharmacy, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Yu Li

  3. Department of Radiology, The Changzhou Road Community Health Service Center of Hedong District, Tianjin, 300250, China

    Xiuna Ma

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  1. Gang Wang
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11010_2020_3764_MOESM1_ESM.tif

Supplemental Fig. 1. Circ_0124644 promoted the ox-LDL-induced colony formation inhibition in HUVECs. The colony formation assay was administrated to analyze the function of si-circ_0124644 or circ_0124644 on colony formation capacity in ox-LDL-treated HUVECs. (TIF 811 kb)

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Wang, G., Li, Y., Liu, Z. et al. Circular RNA circ_0124644 exacerbates the ox-LDL-induced endothelial injury in human vascular endothelial cells through regulating PAPP-A by acting as a sponge of miR-149-5p. Mol Cell Biochem 471, 51–61 (2020). https://doi.org/10.1007/s11010-020-03764-0

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