Circ-UBR4 Regulates the Proliferation, Migration, Inflammation, and Apoptosis in Ox-LDL-induced Vascular Smooth Muscle Cells Via MiR-515-5p/IGF2 Axis

Overview

Journal Open Med (Wars)

Specialty General Medicine

Date 2023 Sep 11

PMID 37693837

Authors

Liuliu Feng

Tianhua Liu

Jun Shi

Yu Wang

Yuya Yang

Wenyin Xiao

Yanyan Bai

Affiliations

Soon will be listed here.

Abstract

The aim of our study is to disclose the role and underlying molecular mechanisms of circular RNA ubiquitin protein ligase E3 component -recognin 4 (circ-UBR4) in atherosclerosis (AS). Our data showed that circ-UBR4 expression was upregulated in AS patients and oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) compared with healthy volunteer and untreated VSMCs. In addition, ox-LDL stimulated proliferation, migration, and inflammation but decreased apoptosis in VSMCs, which were overturned by the inhibition of circ-UBR4. miR-515-5p was sponged by circ-UBR4, and its inhibitor reversed the inhibitory effect of circ-UBR4 knockdown on proliferation, migration, and inflammation in ox-LDL-induced VSMCs. Insulin-like growth factor2 (IGF2) was a functional target of miR-515-5p, and overexpression of IGF2 reversed the suppressive effect of miR-515-5p on ox-LDL-stimulated VSMCs proliferation, migration, and inflammation. Collectively, circ-UBR4 knockdown decreased proliferation, migration, and inflammation but stimulated apoptosis in ox-LDL-induced VSMCs by targeting the miR-515-5p/IGF2 axis.

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References

Nordin M, Bergman D, Halje M, Engstrom W, Ward A . Epigenetic regulation of the Igf2/H19 gene cluster. Cell Prolif. 2014; 47(3):189-99. PMC: 6496486. DOI: 10.1111/cpr.12106. View

Fredman G, Tabas I . Boosting Inflammation Resolution in Atherosclerosis: The Next Frontier for Therapy. Am J Pathol. 2017; 187(6):1211-1221. PMC: 5455064. DOI: 10.1016/j.ajpath.2017.01.018. View

Torres N, Guevara-Cruz M, Velazquez-Villegas L, Tovar A . Nutrition and Atherosclerosis. Arch Med Res. 2015; 46(5):408-26. DOI: 10.1016/j.arcmed.2015.05.010. View

Sun Y, Chen D, Cao L, Zhang R, Zhou J, Chen H . MiR-490-3p modulates the proliferation of vascular smooth muscle cells induced by ox-LDL through targeting PAPP-A. Cardiovasc Res. 2013; 100(2):272-9. DOI: 10.1093/cvr/cvt172. View

Feng Z, Zhu Y, Zhang J, Yang W, Chen Z, Li B . Hsa-circ_0010283 Regulates Oxidized Low-Density Lipoprotein-Induced Proliferation and Migration of Vascular Smooth Muscle Cells by Targeting the miR-133a-3p/Pregnancy-Associated Plasma Protein A Axis. Circ J. 2020; 84(12):2259-2269. DOI: 10.1253/circj.CJ-20-0345. View

Rhoads J, Major A . How Oxidized Low-Density Lipoprotein Activates Inflammatory Responses. Crit Rev Immunol. 2019; 38(4):333-342. PMC: 6527110. DOI: 10.1615/CritRevImmunol.2018026483. View

Zhang X, Zhou J, Xue D, Li Z, Liu Y, Dong L . MiR-515-5p acts as a tumor suppressor via targeting TRIP13 in prostate cancer. Int J Biol Macromol. 2019; 129:227-232. DOI: 10.1016/j.ijbiomac.2019.01.127. View

Zhang L, Cheng H, Yue Y, Li S, Zhang D, He R . H19 knockdown suppresses proliferation and induces apoptosis by regulating miR-148b/WNT/β-catenin in ox-LDL -stimulated vascular smooth muscle cells. J Biomed Sci. 2018; 25(1):11. PMC: 5804091. DOI: 10.1186/s12929-018-0418-4. View

Pardo O, Castellano L, Munro C, Hu Y, Mauri F, Krell J . miR-515-5p controls cancer cell migration through MARK4 regulation. EMBO Rep. 2016; 17(4):570-84. PMC: 4818771. DOI: 10.15252/embr.201540970. View

10.

Barquera S, Pedroza-Tobias A, Medina C, Hernandez-Barrera L, Bibbins-Domingo K, Lozano R . Global Overview of the Epidemiology of Atherosclerotic Cardiovascular Disease. Arch Med Res. 2015; 46(5):328-38. DOI: 10.1016/j.arcmed.2015.06.006. View

11.

Li S, Hu Y, Zhao J, Ma X, Wu S, Lu J . Ox-LDL upregulates CRP expression through the IGF2 pathway in THP-1 macrophages. Inflammation. 2014; 38(2):576-83. DOI: 10.1007/s10753-014-9964-4. View

12.

Guo M, Yan R, Ji Q, Yao H, Sun M, Duan L . IFN regulatory Factor-1 induced macrophage pyroptosis by modulating m6A modification of circ_0029589 in patients with acute coronary syndrome. Int Immunopharmacol. 2020; 86:106800. DOI: 10.1016/j.intimp.2020.106800. View

13.

Yang L, Yang F, Zhao H, Wang M, Zhang Y . Circular RNA circCHFR Facilitates the Proliferation and Migration of Vascular Smooth Muscle via miR-370/FOXO1/Cyclin D1 Pathway. Mol Ther Nucleic Acids. 2019; 16:434-441. PMC: 6488807. DOI: 10.1016/j.omtn.2019.02.028. View

14.

Back M, Hansson G . Anti-inflammatory therapies for atherosclerosis. Nat Rev Cardiol. 2015; 12(4):199-211. DOI: 10.1038/nrcardio.2015.5. View

15.

Wu X, Zheng X, Cheng J, Zhang K, Ma C . LncRNA TUG1 regulates proliferation and apoptosis by regulating miR-148b/IGF2 axis in ox-LDL-stimulated VSMC and HUVEC. Life Sci. 2020; 243:117287. DOI: 10.1016/j.lfs.2020.117287. View

16.

Yu H, Zhao L, Zhao Y, Fei J, Zhang W . Circular RNA circ_0029589 regulates proliferation, migration, invasion, and apoptosis in ox-LDL-stimulated VSMCs by regulating miR-424-5p/IGF2 axis. Vascul Pharmacol. 2020; 135:106782. DOI: 10.1016/j.vph.2020.106782. View

17.

Huang F, Dang J, Zhang S, Cheng Z . Circular RNA hsa_circ_0008039 promotes proliferation, migration and invasion of breast cancer cells through upregulating CBX4 via sponging miR-515-5p. Eur Rev Med Pharmacol Sci. 2020; 24(4):1887-1898. DOI: 10.26355/eurrev_202002_20367. View

18.

Zhang F, Zhang R, Zhang X, Wu Y, Li X, Zhang S . Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of atherosclerosis in rabbits. Aging (Albany NY). 2018; 10(9):2266-2283. PMC: 6188486. DOI: 10.18632/aging.101541. View

19.

Ni J, Zheng H, Ou Y, Tao Y, Wang Z, Song L . miR-515-5p suppresses HCC migration and invasion via targeting IL6/JAK/STAT3 pathway. Surg Oncol. 2020; 34:113-120. DOI: 10.1016/j.suronc.2020.03.003. View

20.

Ding P, Ding Y, Tian Y, Lei X . Circular RNA circ_0010283 regulates the viability and migration of oxidized low‑density lipoprotein‑induced vascular smooth muscle cells via an miR‑370‑3p/HMGB1 axis in atherosclerosis. Int J Mol Med. 2020; 46(4):1399-1408. PMC: 7447304. DOI: 10.3892/ijmm.2020.4703. View