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Circ_0090231 knockdown protects vascular smooth muscle cells from ox-LDL-induced proliferation, migration and invasion via miR-942-5p/PPM1B axis during atherosclerosis

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Abstract

Atherosclerosis (AS) is a dominant pathological basis of cardiovascular disease. Circular RNAs (circRNAs) have been proposed to have crucial functions in regulating pathological progressions of AS. Hence, the aim of this study was to investigate the potential function of circ_0090231 in AS progression. Oxidized low densitylipoprotein (ox-LDL)-challenged vascular smooth muscle cells (VSMCs) were used for in vitro functional analysis. Levels of genes and proteins were measured by qRT-PCR and Western blot. The proliferation, migration and invasion were assessed using cell counting kit-8, 5-ethynyl-2’-deoxyuridine, and transwell assays. The interaction between miR-942-5p and circ_0090231 or PPM1B (Protein Phosphatase, Mg2+/Mn2+ Dependent 1B) was evaluated by dual-luciferase reporter and pull-down assays. Circ_0090231 is a stable circRNA, and was increased in the serum of AS patients and ox-LDL-challenged VSMCs. Functionally, silencing of circ_0090231 could reverse ox-LDL-induced proliferation, migration and invasion in VSMCs. Mechanistically, circ_0090231 directly targeted miR-942-5p, and PPM1B was a target of miR-942-5p. Besides, circ_0090231 sequestered miR-942-5p to release PPM1B expression, suggesting the circ_0090231/miR-942-5p/PPM1B axis. Further rescue experiments showed that miR-942-5p inhibition or ectopic overexpression of PPM1B dramatically attenuated the suppressing influences of circ_0090231 knockdown on VSMC proliferative, migratory and invasive abilities under ox-LDL treatment. Silencing of circ_0090231 could reverse ox-LDL-induced proliferation, migration and invasion in VSMCs via miR-942-5p/PPM1B axis, providing a theoretical basis for elucidating the mechanism of AS process.

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Data availability

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author notes

  1. Jian Yang and Xiangyan Li equally contributed to this work.

Authors and Affiliations

  1. Department of Ultrasonic Imaging, Affiliated Renhe Hospital of China Three Gorges University, No.410, Yiling Avenue, Yichang, 443001, China

    Jian Yang, Yuming Zhang, Pengfei Che, Wei Qin, Xuecui Wu & Bing Hu

  2. Department of Interventional Catheter Lab, Affiliated Renhe Hospital of China Three Gorges University, Yichang, 443001, China

    Xiangyan Li

  3. Department of Radiology, Affiliated Renhe Hospital of China Three Gorges University, Yichang, 443001, China

    Yue Liu

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  1. Jian Yang
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Contributions

BH designed and supervised the study. JY and XL conducted the experiments and drafted the manuscript. YZ and PC collected and analyzed the data. WQ contributed the methodology. XW and YL operated the software and edited the manuscript. All authors reviewed the manuscript.

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Correspondence to Bing Hu.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethics approval

The procedure of the experiment was approved by the Ethics Committee of Affiliated Renhe Hospital of China Three Gorges University and was carried out according to the guidelines of Declaration of Helsinki. Written informed consent was collected from all participants before sample collection.

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The procedure of the experiment was approved by the Ethics Committee of Affiliated Renhe Hospital of China Three Gorges University and was carried out according to the guidelines of Declaration of Helsinki. Written informed consent was collected from all participants before sample collection.

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Yang, J., Li, X., Zhang, Y. et al. Circ_0090231 knockdown protects vascular smooth muscle cells from ox-LDL-induced proliferation, migration and invasion via miR-942-5p/PPM1B axis during atherosclerosis. Mol Cell Biochem (2023). https://doi.org/10.1007/s11010-023-04811-2

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