MiR-128-3p Inhibits Vascular Smooth Muscle Cell Proliferation and Migration by Repressing FOXO4/MMP9 Signaling Pathway

Overview

Journal Mol Med

Publisher Biomed Central

Specialties General Medicine
Molecular Biology

Date 2020 Nov 26

PMID 33238881

Citations 9

Authors

Chuan Qu

Xin Liu

Yan Guo

Yuhong Fo

Xiuhuan Chen

Jining Zhou

Bo Yang

Affiliations

Soon will be listed here.

Abstract

Background: MicroRNAs (miRNAs) have been identified as important participants in the development of atherosclerosis (AS). The present study explored the role of miR-128-3p in the dysfunction of vascular smooth muscle cells (VSMCs) and the underlying mechanism.

Methods: Human VSMCs and ApoE knockout (ApoE) C57BL/6J mice were used to establish AS cell and animal models, respectively. Expression levels of miR-128-3p, forkhead box O4 (FOXO4) and matrix metallopeptidase 9 (MMP9) were detected using qRT-PCR and Western blot, respectively. CCK-8, BrdU, and Transwell assays as well as flow cytometry analysis were performed to detect the proliferation, migration and apoptosis of VSMCs. Levels of inflammatory cytokines and lipids in human VSMCs, mice serum and mice VSMCs were also determined. The binding site between miR-128-3p and 3'UTR of FOXO4 was confirmed using luciferase reporter gene assay.

Results: MiR-128-3p was found to be decreased in AS patient serum, ox-LDL-treated VSMCs, AS mice serum and VSMCs of AS mice. Transfection of miR-128-3p mimics suppressed the proliferation and migration of VSMCs, accompanied by the promoted apoptosis and the decreased levels of inflammatory cytokines. Further experiments confirmed the interaction between miR-128-3p and FOXO4. Augmentation of FOXO4 or MMP9 reversed the effects of miR-128-3p. Besides, miR-128-3p inhibited triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) but increased high-density lipoprotein cholesterol (HDL-C) in the serum of AS mice.

Conclusion: MiR-128-3p repressed the proliferation and migration of VSMCs through inhibiting the expressions of FOXO4 and MMP9.

Citing Articles

Retinopathy of Prematurity and MicroRNAs.

Albanese G, Visioli G, Alisi L, Armentano M, Giovannetti F, Lucchino L Biomedicines. 2025; 13(2).

PMID: 40002813 PMC: 11852721. DOI: 10.3390/biomedicines13020400.

The role of miR-128 and MDFI in cardiac hypertrophy and heart failure: Mechanistic.

Yanjun S, Yunfen G, Haoyi Y, Zhe W, Jiapei Q J Cell Mol Med. 2024; 28(14):e18546.

PMID: 39046458 PMC: 11268151. DOI: 10.1111/jcmm.18546.

Fetal Brain-Derived Exosomal miRNAs from Maternal Blood: Potential Diagnostic Biomarkers for Fetal Alcohol Spectrum Disorders (FASDs).

Darbinian N, Hampe M, Martirosyan D, Bajwa A, Darbinyan A, Merabova N Int J Mol Sci. 2024; 25(11).

PMID: 38892014 PMC: 11172088. DOI: 10.3390/ijms25115826.

miR-128-3p Regulates Follicular Granulosa Cell Proliferation and Apoptosis by Targeting the Growth Hormone Secretagogue Receptor.

Dong S, Jiang S, Hou B, Li Y, Sun B, Guo Y Int J Mol Sci. 2024; 25(5).

PMID: 38473968 PMC: 10931543. DOI: 10.3390/ijms25052720.

MicroRNAs-associated with FOXO3 in cellular senescence and other stress responses.

Khor Y, Wong P Biogerontology. 2023; 25(1):23-51.

PMID: 37646881 DOI: 10.1007/s10522-023-10059-6.

References

Fu C, Li D, Zhang X, Liu N, Chi G, Jin X . LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway. Neurotherapeutics. 2018; 15(4):1139-1157. PMC: 6277294. DOI: 10.1007/s13311-018-0649-9. View

Zhao X, Jin Y, Li L, Xu L, Tang Z, Qi Y . MicroRNA-128-3p aggravates doxorubicin-induced liver injury by promoting oxidative stress via targeting Sirtuin-1. Pharmacol Res. 2019; 146:104276. DOI: 10.1016/j.phrs.2019.104276. View

Zhao J, Li D, Fang L . MiR-128-3p suppresses breast cancer cellular progression via targeting LIMK1. Biomed Pharmacother. 2019; 115:108947. DOI: 10.1016/j.biopha.2019.108947. View

Gong C, Ai J, Fan Y, Gao J, Liu W, Feng Q . NCAPG Promotes The Proliferation Of Hepatocellular Carcinoma Through PI3K/AKT Signaling. Onco Targets Ther. 2019; 12:8537-8552. PMC: 6801502. DOI: 10.2147/OTT.S217916. View

Gholipour S, Sewell R, Lorigooini Z, Rafieian-Kopaei M . Medicinal Plants and Atherosclerosis: A Review on Molecular Aspects. Curr Pharm Des. 2018; 24(26):3123-3131. DOI: 10.2174/1381612824666180911121525. View

Lim S, Park S . Role of vascular smooth muscle cell in the inflammation of atherosclerosis. BMB Rep. 2014; 47(1):1-7. PMC: 4163848. DOI: 10.5483/bmbrep.2014.47.1.285. View

Liu H, Wang L, Weng X, Chen H, Du Y, Diao C . Inhibition of Brd4 alleviates renal ischemia/reperfusion injury-induced apoptosis and endoplasmic reticulum stress by blocking FoxO4-mediated oxidative stress. Redox Biol. 2019; 24:101195. PMC: 6475721. DOI: 10.1016/j.redox.2019.101195. View

Siegel-Axel D, Daub K, Seizer P, Lindemann S, Gawaz M . Platelet lipoprotein interplay: trigger of foam cell formation and driver of atherosclerosis. Cardiovasc Res. 2008; 78(1):8-17. DOI: 10.1093/cvr/cvn015. View

Wu Y, Zhang S, Cui J, Liu F . Long Noncoding RNA XR007793 Regulates Proliferation and Migration of Vascular Smooth Muscle Cell via Suppressing miR-23b. Med Sci Monit. 2018; 24:5895-5903. PMC: 6119354. DOI: 10.12659/MSM.908902. View

10.

Li H, Liang J, Castrillon D, DePinho R, Olson E, Liu Z . FoxO4 regulates tumor necrosis factor alpha-directed smooth muscle cell migration by activating matrix metalloproteinase 9 gene transcription. Mol Cell Biol. 2007; 27(7):2676-86. PMC: 1899894. DOI: 10.1128/MCB.01748-06. View

11.

Bejarano J, Navarro-Marquez M, Morales-Zavala F, Morales J, Garcia-Carvajal I, Araya-Fuentes E . Nanoparticles for diagnosis and therapy of atherosclerosis and myocardial infarction: evolution toward prospective theranostic approaches. Theranostics. 2018; 8(17):4710-4732. PMC: 6160774. DOI: 10.7150/thno.26284. View

12.

Liu J, Wang S, Zhang Q, Li X, Xu S . Selenomethionine alleviates LPS-induced chicken myocardial inflammation by regulating the miR-128-3p-p38 MAPK axis and oxidative stress. Metallomics. 2019; 12(1):54-64. DOI: 10.1039/c9mt00216b. View

13.

Wang W, Zhou P, Hu W . Overexpression of FOXO4 induces apoptosis of clear-cell renal carcinoma cells through downregulation of Bim. Mol Med Rep. 2016; 13(3):2229-34. DOI: 10.3892/mmr.2016.4789. View

14.

Chen D, Hui L, Zhang X, Chang Q . NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in macrophages through inhibiting miR-128. J Cell Biochem. 2018; 120(2):2493-2501. DOI: 10.1002/jcb.27541. View

15.

Liu X, Ma B, Liu S, Liu J, Ma B . Long noncoding RNA LINC00341 promotes the vascular smooth muscle cells proliferation and migration via miR-214/FOXO4 feedback loop. Am J Transl Res. 2019; 11(3):1835-1842. PMC: 6456561. View

16.

Moss J, Ramji D . Nutraceutical therapies for atherosclerosis. Nat Rev Cardiol. 2016; 13(9):513-32. PMC: 5228762. DOI: 10.1038/nrcardio.2016.103. View

17.

Farina F, Hall I, Serio S, Zani S, Climent M, Salvarani N . miR-128-3p Is a Novel Regulator of Vascular Smooth Muscle Cell Phenotypic Switch and Vascular Diseases. Circ Res. 2020; 126(12):e120-e135. DOI: 10.1161/CIRCRESAHA.120.316489. View

18.

Wu X, Chen L, Zeb F, Li C, Jiang P, Chen A . Clock-Bmal1 mediates MMP9 induction in acrolein-promoted atherosclerosis associated with gut microbiota regulation. Environ Pollut. 2019; 252(Pt B):1455-1463. DOI: 10.1016/j.envpol.2019.06.042. View

19.

Byon C, Han T, Wu J, Hui S . Txnip ablation reduces vascular smooth muscle cell inflammation and ameliorates atherosclerosis in apolipoprotein E knockout mice. Atherosclerosis. 2015; 241(2):313-21. PMC: 4509824. DOI: 10.1016/j.atherosclerosis.2015.05.020. View

20.

Balzan S, Lubrano V . LOX-1 receptor: A potential link in atherosclerosis and cancer. Life Sci. 2018; 198:79-86. DOI: 10.1016/j.lfs.2018.02.024. View