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MicroRNA‑125a‑mediated regulation of the mevalonate signaling pathway contributes to high glucose‑induced proliferation and migration of vascular smooth muscle cells

  • Authors:
    • Dan Ye
    • Guo‑Hua Lou
    • Ai‑Chun Li
    • Feng‑Qin Dong
    • Guo‑Ping Chen
    • Wei‑Wei Xu
    • Yan‑Ning Liu
    • Shen‑Jiang Hu
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology and Metabolism, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Institute of Cardiology, The First Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
    Copyright: © Ye et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 165-174
    |
    Published online on: April 16, 2020
       https://doi.org/10.3892/mmr.2020.11077
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Abstract

Hyperglycemia contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMC), which are closely associated with atherosclerosis. MicroRNAs (miRNAs/miRs) constitute a novel class of gene regulators, which have important roles in various pathological conditions. The aim of the present study was to identify miRNAs involved in the high glucose (HG)‑induced VSMC phenotype switch, and to investigate the underlying mechanism. miRNA sequencing and reverse transcription‑quantitative PCR results indicated that inhibition of miR‑125a expression increased the migration and proliferation of VSMCs following HG exposure, whereas the overexpression of miR‑125a abrogated this effect. Furthermore, dual‑luciferase reporter assay results identified that 3‑hydroxy‑3-methyglutaryl‑coA reductase (HMGCR), one of the key enzymes in the mevalonate signaling pathway, is a target of miR‑125a. Moreover, HMGCR knockdown, similarly to miR‑125a overexpression, suppressed HG‑induced VSMC proliferation and migration. These results were consistent with those from the miRNA target prediction programs. Using a rat model of streptozotocin‑induced diabetes mellitus, it was demonstrated that miR‑125a expression was gradually downregulated, and that the expressions of key enzymes in the mevalonate signaling pathway in the aortic media were dysregulated after several weeks. In addition, it was found that HG‑induced excessive activation of the mevalonate signaling pathway in VSMCs was suppressed following transfection with a miR‑125a mimic. Therefore, the present results suggest that decreased miR‑125a expression contributed to HG‑induced VSMC proliferation and migration via the upregulation of HMGCR expression. Thus, miR‑125a‑mediated regulation of the mevalonate signaling pathway may be associated with atherosclerosis.
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1 

Atkinson MA, Eisenbarth GS and Michels AW: Type 1 diabetes. Lancet. 383:69–82. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Chatterjee S, Khunti K and Davies MJ: Type 2 diabetes. Lancet. 389:2239–2251. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Gilbert RE and Krum H: Heart failure in diabetes: Effects of anti-hyperglycaemic drug therapy. Lancet. 385:2107–2117. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Katakami N: Mechanism of Development of atherosclerosis and cardiovascular disease in diabetes mellitus. J Atheroscler Thromb. 25:27–39. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Low Wang CC, Hess CN, Hiatt WR and Goldfine AB: Clinical update: Cardiovascular disease in diabetes mellitus: Atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus-mechanisms, management, and clinical considerations. Circulation. 133:2459–2502. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Shi L, Ji Y, Jiang X, Zhou L, Xu Y, Li Y, Jiang W, Meng P and Liu X: Liraglutide attenuates high glucose-induced abnormal cell migration, proliferation, and apoptosis of vascular smooth muscle cells by activating the GLP-1 receptor, and inhibiting ERK1/2 and PI3K/Akt signaling pathways. Cardiovasc Diabetol. 14:182015. View Article : Google Scholar : PubMed/NCBI

7 

Carthew RW and Sontheimer EJ: Origins and mechanisms of miRNAs and siRNAs. Cell. 136:642e552009. View Article : Google Scholar

8 

He L and Hannon GJ: MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet. 5:522–531. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Ding Y, Sun X and Shan PF: MicroRNAs and cardiovascular disease in diabetes mellitus. Biomed Res Int. 2017:40803642017. View Article : Google Scholar : PubMed/NCBI

10 

Rudijanto A: The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis. Acta Med Indones. 39:86–93. 2007.PubMed/NCBI

11 

Chait A and Bornfeldt KE: Diabetes and atherosclerosis: Is there a role for hyperglycemia? J Lipid Res. 50 (Suppl):S335–S339. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Chen GP, Zhang XQ, Wu T, Li L, Han J and Du CQ: Alteration of mevalonate pathway in proliferated vascular smooth muscle from diabetic mice: Possible role in high-glucose-induced atherogenic process. J Diabetes Res. 2015:3792872015. View Article : Google Scholar : PubMed/NCBI

13 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, Novelli M and Ribes G: Experimental NIDDM: Development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes. 47:224–229. 1998. View Article : Google Scholar : PubMed/NCBI

15 

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF and Turner RC: Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28:412–419. 1985. View Article : Google Scholar : PubMed/NCBI

16 

Hwang HW and Mendell JT: MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 96:776–780. 2007.PubMed/NCBI

17 

Ye D, Zhang T, Lou G and Liu Y: Role of miR-223 in the pathophysiology of liver diseases. Exp Mol Med. 50:1282018. View Article : Google Scholar : PubMed/NCBI

18 

Maegdefessel L, Rayner KJ and Leeper NJ: MicroRNA regulation of vascular smooth muscle function and phenotype: Early career committee contribution. Arterioscler Thromb Vasc Biol. 35:2–6. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Santovito D, Egea V and Weber C: Small but smart: MicroRNAs orchestrate atherosclerosis development and progression. Biochim Biophys Acta 1861 (12 Pt B). 2075–2086. 2016.

20 

Ji R, Cheng Y, Yue J, Yang J, Liu X, Chen H, Dean DB and Zhang C: MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res. 100:1579–1588. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Liu X, Cheng Y, Zhang S, Lin Y, Yang J and Zhang C: A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res. 104:476–487. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Leeper NJ, Raiesdana A, Kojima Y, Chun HJ, Azuma J, Maegdefessel L, Kundu RK, Quertermous T, Tsao PS and Spin JM: MicroRNA-26a is a novel regulator of vascular smooth muscle cell function. J Cell Physiol. 226:1035–1043. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Xu J, Li L, Yun HF and Han YS: MiR-138 promotes smooth muscle cells proliferation and migration in db/db mice through down-regulation of SIRT1. Biochem Biophys Res Commun. 463:1159–1164. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN and Srivastava D: miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. 460:705–710. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Torella D, Iaconetti C, Catalucci D, Ellison GM, Leone A, Waring CD, Bochicchio A, Vicinanza C, Aquila I, Curcio A, et al: MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and vascular remodeling in vivo. Circ Res. 109:880–893. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Yang J, Chen L, Ding J, Fan Z, Li S, Wu H, Zhang J, Yang C, Wang H, Zeng P and Yang J: MicroRNA-24 inhibits high glucose-induced vascular smooth muscle cell proliferation and migration by targeting HMGB1. Gene. 586:268–273. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Chen M, Zhang Y, Li W and Yang J: MicroRNA-145 alleviates high glucose-induced proliferation and migration of vascular smooth muscle cells through targeting ROCK1. Biomed Pharmacother. 99:81–86. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Bi Q, Tang S, Xia L, Du R, Fan R, Gao L, Jin J, Liang S, Chen Z, Xu G, et al: Ectopic expression of MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGF. PLoS One. 7:e401692012. View Article : Google Scholar : PubMed/NCBI

29 

Sun YM, Lin KY and Chen YQ: Diverse functions of miR-125 family in different cell contexts. J Hematol Oncol. 6:62013. View Article : Google Scholar : PubMed/NCBI

30 

Zhang Y, Zhang D, Lv J, Wang S and Zhang Q: MiR-125a-5p suppresses bladder cancer progression through targeting FUT4. Biomed Pharmacother. 108:1039–1047. 2018. View Article : Google Scholar : PubMed/NCBI

31 

Cai M, Chen Q, Shen J, Lv C and Cai L: Epigenetic silenced miR-125a-5p could be self-activated through targeting Suv39H1 in gastric cancer. J Cell Mol Med. 22:4721–4731. 2018. View Article : Google Scholar : PubMed/NCBI

32 

Yan L, Yu MC, Gao GL, Liang HW, Zhou XY, Zhu ZT, Zhang CY, Wang YB and Chen X: MiR-125a-5p functions as a tumour suppressor in breast cancer by downregulating BAP1. J Cell Biochem. 119:8773–8783. 2018. View Article : Google Scholar : PubMed/NCBI

33 

Goldstein JL and Brown MS: Regulation of the mevalonate pathway. Nature. 343:425–430. 1990. View Article : Google Scholar : PubMed/NCBI

34 

Buhaescu I and Izzedine H: Mevalonate pathway: A review of clinical and therapeutical implications. Clin Biochem. 40:575–584. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Han J, Jiang DM, Du CQ and Hu SJ: Alteration of enzyme expressions in mevalonate pathway: Possible role for cardiovascular remodeling in spontaneously hypertensive rats. Circ J. 75:1409–1417. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Chen GP, Zhang XQ, Wu T, Han J and Ye D: Inhibition of farnesyl pyrophosphate synthase attenuates high glucose-induced vascular smooth muscle cells proliferation. Mol Med Rep. 15:3153–3160. 2017. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ye D, Lou GH, Li AC, Dong FQ, Chen GP, Xu WW, Liu YN and Hu SJ: MicroRNA‑125a‑mediated regulation of the mevalonate signaling pathway contributes to high glucose‑induced proliferation and migration of vascular smooth muscle cells. Mol Med Rep 22: 165-174, 2020.
APA
Ye, D., Lou, G., Li, A., Dong, F., Chen, G., Xu, W. ... Hu, S. (2020). MicroRNA‑125a‑mediated regulation of the mevalonate signaling pathway contributes to high glucose‑induced proliferation and migration of vascular smooth muscle cells. Molecular Medicine Reports, 22, 165-174. https://doi.org/10.3892/mmr.2020.11077
MLA
Ye, D., Lou, G., Li, A., Dong, F., Chen, G., Xu, W., Liu, Y., Hu, S."MicroRNA‑125a‑mediated regulation of the mevalonate signaling pathway contributes to high glucose‑induced proliferation and migration of vascular smooth muscle cells". Molecular Medicine Reports 22.1 (2020): 165-174.
Chicago
Ye, D., Lou, G., Li, A., Dong, F., Chen, G., Xu, W., Liu, Y., Hu, S."MicroRNA‑125a‑mediated regulation of the mevalonate signaling pathway contributes to high glucose‑induced proliferation and migration of vascular smooth muscle cells". Molecular Medicine Reports 22, no. 1 (2020): 165-174. https://doi.org/10.3892/mmr.2020.11077
Copy and paste a formatted citation
x
Spandidos Publications style
Ye D, Lou GH, Li AC, Dong FQ, Chen GP, Xu WW, Liu YN and Hu SJ: MicroRNA‑125a‑mediated regulation of the mevalonate signaling pathway contributes to high glucose‑induced proliferation and migration of vascular smooth muscle cells. Mol Med Rep 22: 165-174, 2020.
APA
Ye, D., Lou, G., Li, A., Dong, F., Chen, G., Xu, W. ... Hu, S. (2020). MicroRNA‑125a‑mediated regulation of the mevalonate signaling pathway contributes to high glucose‑induced proliferation and migration of vascular smooth muscle cells. Molecular Medicine Reports, 22, 165-174. https://doi.org/10.3892/mmr.2020.11077
MLA
Ye, D., Lou, G., Li, A., Dong, F., Chen, G., Xu, W., Liu, Y., Hu, S."MicroRNA‑125a‑mediated regulation of the mevalonate signaling pathway contributes to high glucose‑induced proliferation and migration of vascular smooth muscle cells". Molecular Medicine Reports 22.1 (2020): 165-174.
Chicago
Ye, D., Lou, G., Li, A., Dong, F., Chen, G., Xu, W., Liu, Y., Hu, S."MicroRNA‑125a‑mediated regulation of the mevalonate signaling pathway contributes to high glucose‑induced proliferation and migration of vascular smooth muscle cells". Molecular Medicine Reports 22, no. 1 (2020): 165-174. https://doi.org/10.3892/mmr.2020.11077
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