LncRNA ZFAS1 Promotes the Ox-LDL Induced Proliferation, Invasion and Migration of Vascular Smooth Muscle Cells

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2021 Jun 21

PMID 34149881

Citations 3

Authors

Hao Wang

Huajie Hu

Junjie Ma

Yafeng Jiang

Ruifei Cheng

Affiliations

Soon will be listed here.

Abstract

Atherosclerosis is a chronic progressive inflammatory vascular disease. The dysfunction of vascular smooth muscle cells (VSMCs) induced by oxidized low-density lipoprotein (ox-LDL) contributes to the formation of atherosclerotic lesions. Additionally, upregulation of the long non-coding RNA zinc finger antisense 1 (ZFAS1) was observed in the plaques of patients with atherosclerosis. The aim of the present study was to explore the functional role of ZFAS1 in atherosclerosis progression. Reverse transcription-quantitative PCR was performed to analyze ZFAS1 mRNA expression, and western blotting was performed to determine the protein expression levels of Ki67, proliferating cell nuclear antigen (PCNA), matrix metallopeptidase (MMP)2 and MMP9. The Cell Counting Kit-8 assay was used to test cell viability. Finally, wound healing and Transwell chamber assays were performed to evaluate cell migration and invasion, respectively. The current findings demonstrated that ZFAS1 expression was upregulated by ox-LDL stimulation in VSMCs. Moreover, ZFAS1 overexpression promoted the ox-LDL-induced proliferation, migration and invasion of VSMCs, and upregulated the expression levels of proteins associated with cellular proliferation (Ki67 and PCNA), migration and invasion (MMP2 and 9). By contrast, ZFAS1-knockdown inhibited the proliferation, migration and invasion of VSMCs, and suppressed cell proliferation-, migration- and invasion-associated protein expression. In conclusion, ZFAS1 promoted the ox-LDL-induced proliferation, invasion and migration of VSMCs. Thus, ZFAS1 may represent a novel biomarker for dysfunction of VSMCs in the pathological condition of atherosclerosis.

Citing Articles

An update on the molecular mechanisms of ZFAS1 as a prognostic, diagnostic, or therapeutic biomarker in cancers.

Mehrab Mohseni M, Zamani H, Momeni M, Shirvani-Farsani Z Discov Oncol. 2024; 15(1):219.

PMID: 38856786 PMC: 11164845. DOI: 10.1007/s12672-024-01078-x.

Circ_0004872 deficiency attenuates ox-LDL-induced vascular smooth muscle cell dysfunction by miR-424-5p-dependent regulation of FRS2.

Qian P, Cao X, Zhang Q, Gao M, Liu X, Yan L Mol Cell Biochem. 2024; 479(12):3425-3435.

PMID: 38376663 DOI: 10.1007/s11010-024-04929-x.

Role of miR-181b/Notch1 Axis in circ_TNPO1 Promotion of Proliferation and Migration of Atherosclerotic Vascular Smooth Muscle Cells.

Chen M, Li F, Jiang Q, Zhang W, Li Z, Tang W J Healthc Eng. 2022; 2022:4086935.

PMID: 35388333 PMC: 8977319. DOI: 10.1155/2022/4086935.

References

Zhang Y, Jiao L, Sun L, Li Y, Gao Y, Xu C . LncRNA as a SERCA2a Inhibitor to Cause Intracellular Ca Overload and Contractile Dysfunction in a Mouse Model of Myocardial Infarction. Circ Res. 2018; 122(10):1354-1368. PMC: 5959220. DOI: 10.1161/CIRCRESAHA.117.312117. View

Liu M, Song Y, Han Z . Study on the effect of LncRNA AK094457 on OX-LDL induced vascular smooth muscle cells. Am J Transl Res. 2019; 11(9):5623-5633. PMC: 6789286. View

Wei M, Liu Y, Zheng M, Wang L, Ma F, Qi Y . Upregulation of Protease-Activated Receptor 2 Promotes Proliferation and Migration of Human Vascular Smooth Muscle Cells (VSMCs). Med Sci Monit. 2019; 25:8854-8862. PMC: 6883764. DOI: 10.12659/MSM.917865. View

Bennett M, Sinha S, Owens G . Vascular Smooth Muscle Cells in Atherosclerosis. Circ Res. 2016; 118(4):692-702. PMC: 4762053. DOI: 10.1161/CIRCRESAHA.115.306361. View

Wang J, Uryga A, Reinhold J, Figg N, Baker L, Finigan A . Vascular Smooth Muscle Cell Senescence Promotes Atherosclerosis and Features of Plaque Vulnerability. Circulation. 2015; 132(20):1909-19. DOI: 10.1161/CIRCULATIONAHA.115.016457. View

Guo F, Wu Q, Li P, Zheng L, Ye S, Dai X . The role of the LncRNA-FA2H-2-MLKL pathway in atherosclerosis by regulation of autophagy flux and inflammation through mTOR-dependent signaling. Cell Death Differ. 2019; 26(9):1670-1687. PMC: 6748100. DOI: 10.1038/s41418-018-0235-z. View

Wang X, Jin Q, Wang X, Chen W, Cai Z . LncRNA ZFAS1 promotes proliferation and migration and inhibits apoptosis in nasopharyngeal carcinoma via the PI3K/AKT pathway in vitro. Cancer Biomark. 2019; 26(2):171-182. DOI: 10.3233/CBM-182080. View

Zhao X, Zheng B, Wen Y, Sun Y, Wen J, Zhang X . Salvianolic acid B inhibits Ang II-induced VSMC proliferation in vitro and intimal hyperplasia in vivo by downregulating miR-146a expression. Phytomedicine. 2019; 58:152754. DOI: 10.1016/j.phymed.2018.11.014. View

Ye Z, Yang S, Xia Y, Hu R, Chen S, Li B . LncRNA MIAT sponges miR-149-5p to inhibit efferocytosis in advanced atherosclerosis through CD47 upregulation. Cell Death Dis. 2019; 10(2):138. PMC: 6372637. DOI: 10.1038/s41419-019-1409-4. View

10.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

11.

Farina P, Tabouret E, Lehmann P, Barrie M, Petrirena G, Campello C . Relationship between magnetic resonance imaging characteristics and plasmatic levels of MMP2 and MMP9 in patients with recurrent high-grade gliomas treated by Bevacizumab and Irinotecan. J Neurooncol. 2017; 132(3):433-437. DOI: 10.1007/s11060-017-2385-0. View

12.

Mathy N, Chen X . Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses. J Biol Chem. 2017; 292(30):12375-12382. PMC: 5535013. DOI: 10.1074/jbc.R116.760884. View

13.

Misra A, Feng Z, Chandran R, Kabir I, Rotllan N, Aryal B . Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells. Nat Commun. 2018; 9(1):2073. PMC: 5970166. DOI: 10.1038/s41467-018-04447-7. View

14.

Harman J, Jorgensen H . The role of smooth muscle cells in plaque stability: Therapeutic targeting potential. Br J Pharmacol. 2019; 176(19):3741-3753. PMC: 6780045. DOI: 10.1111/bph.14779. View

15.

Han S, Li D, Xiao M . LncRNA ZFAS1 serves as a prognostic biomarker to predict the survival of patients with ovarian cancer. Exp Ther Med. 2019; 18(6):4673-4681. PMC: 6880189. DOI: 10.3892/etm.2019.8135. View

16.

Meng Q, Zhang R, Ding W, Mao B . Long noncoding RNA ZFAS1 promotes cell proliferation and tumor growth by upregulating LIN28 in cervical carcinoma. Minerva Med. 2019; 111(5):511-514. DOI: 10.23736/S0026-4806.19.06123-8. View

17.

Kattoor A, Kanuri S, Mehta J . Role of Ox-LDL and LOX-1 in Atherogenesis. Curr Med Chem. 2018; 26(9):1693-1700. DOI: 10.2174/0929867325666180508100950. View

18.

Zeng Z, Zhao G, Rao C, Hua G, Yang M, Miao X . Knockdown of lncRNA ZFAS1-suppressed non-small cell lung cancer progression via targeting the miR-150-5p/HMGA2 signaling. J Cell Biochem. 2019; 121(8-9):3814-3824. DOI: 10.1002/jcb.29542. View

19.

Li N, Deng W, Ma J, Wei B, Guo K, Shen W . Prognostic evaluation of Nanog, Oct4, Sox2, PCNA, Ki67 and E-cadherin expression in gastric cancer. Med Oncol. 2014; 32(1):433. DOI: 10.1007/s12032-014-0433-6. View

20.

Chen L, Yao H, Hui J, Ding S, Fan Y, Pan Y . Global transcriptomic study of atherosclerosis development in rats. Gene. 2016; 592(1):43-48. DOI: 10.1016/j.gene.2016.07.023. View