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MiR-448 promotes vascular smooth muscle cell proliferation and migration in through directly targeting MEF2C

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Abstract

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is a critical process in various cardiovascular diseases such as coronary artery disease (CAD), atherosclerosis, stroke, and hypertension. MicroRNAs (miRNAs) are small, short, and noncoding RNAs that inhibit gene expression through binding to the 3′-UTR (3′ untranslated regions) of target gene mRNAs. We showed that the expression of miR-448 was upregulated in VSMCs from coronary atherosclerotic plaques compared with normal coronary artery tissues. We also found that PDGF-bb promoted VSMCs proliferation and could induce miR-448 expression. Ectopic miR-448 expression induced VSMCs proliferation. Overexpression of miR-448 induced ki-67 mRNA and protein expression. Moreover, we identified MEF2C was a direct target of miR-448 in VSMCs. Overexpression of miR-448 promoted VSMCs migration. Furthermore, overexpression of MEF2C decreased miR-448-induced VSMCs proliferation and migration. These evidences suggested that miR-448 played an important role in the proliferation and migration of VSMCs.

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References

  • Chan MC, Hilyard AC, Wu C, Davis BN, Hill NS, Lal A, Lieberman J, Lagna G, Hata A (2010) Molecular basis for antagonism between PDGF and the TGFbeta family of signalling pathways by control of miR-24 expression. EMBO J 29:559–573

    Article  CAS  Google Scholar 

  • Choe N, Kwon JS, Kim JR, Eom GH, Kim Y, Nam KI, Ahn Y, Kee HJ, Kook H (2013) The microRNA miR-132 targets Lrrfip1 to block vascular smooth muscle cell proliferation and neointimal hyperplasia. Atherosclerosis 229:348–355

    Article  CAS  Google Scholar 

  • Han Y, Liu Y, Zhang H, Wang T, Diao R, Jiang Z, Gui Y, Cai Z (2013): Hsa-miR-125b suppresses bladder cancer development by down-regulating oncogene SIRT7 and oncogenic long noncoding RNA MALAT1. FEBS Letters

  • Karagiannis GS, Weile J, Bader GD, Minta J (2013) Integrative pathway dissection of molecular mechanisms of moxLDL-induced vascular smooth muscle phenotype transformation. BMC Cardiovasc Disord 13:4

    Article  CAS  Google Scholar 

  • Kim MH, Ham O, Lee SY, Choi E, Lee CY, Park JH, Lee J, Seo HH, Seung M, Min PK, Hwang KC (2014) MicroRNA-365 inhibits the proliferation of vascular smooth muscle cells by targeting cyclin D1. J Cell Biochem

  • Kim S, Kang H (2013) miR-15b induced by platelet-derived growth factor signaling is required for vascular smooth muscle cell proliferation. BMB Rep 46:550–554

    Article  CAS  Google Scholar 

  • Li J, Zhao L, He X, Yang T, Yang K (2014) MiR-21 inhibits c-Ski signaling to promote the proliferation of rat vascular smooth muscle cells. Cell Signal 26:724–729

    Article  Google Scholar 

  • Li P, Liu Y, Yi B, Wang G, You X, Zhao X, Summer R, Qin Y, Sun J (2013) MicroRNA-638 is highly expressed in human vascular smooth muscle cells and inhibits PDGF-BB-induced cell proliferation and migration through targeting orphan nuclear receptor NOR1. Cardiovasc Res 99:185–193

    Article  CAS  Google Scholar 

  • Li QQ, Chen ZQ, Cao XX, Xu JD, Xu JW, Chen YY, Wang WJ, Chen Q, Tang F, Liu XP, Xu ZD (2011) Involvement of NF-kappaB/miR-448 regulatory feedback loop in chemotherapy-induced epithelial-mesenchymal transition of breast cancer cells. Cell Death Differ 18:16–25

    Article  Google Scholar 

  • Li Z, Lei H, Luo M, Wang Y, Dong L, Ma Y, Liu C, Song W, Wang F, Zhang J, Shen J, Yu J (2015a) DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer. Gastric Cancer 18:43–54

    Article  CAS  Google Scholar 

  • Li Z, Yu X, Shen J, Chan MT, Wu WK (2015b) MicroRNA in intervertebral disc degeneration. Cell Prolif 48:278–283

    Article  CAS  Google Scholar 

  • Li Z, Yu X, Shen J, Jiang Y (2015c) MicroRNA dysregulation in uveal melanoma: a new player enters the game. Oncotarget

  • Li Z, Yu X, Shen J, Law PT, Chan MT, Wu WK (2015d) MicroRNA expression and its implications for diagnosis and therapy of gallbladder cancer. Oncotarget 6:13914–13924

    Article  Google Scholar 

  • Li Z, Yu X, Shen J, Wu WK, Chan MT (2015e) MicroRNA expression and its clinical implications in Ewing’s sarcoma. Cell Prolif 48:1–6

    Article  Google Scholar 

  • Li Z, Yu X, Wang Y, Shen J, Wu WK, Liang J, Feng F (2015f) By downregulating TIAM1 expression, microRNA-329 suppresses gastric cancer invasion and growth. Oncotarget 6:17559–17569

    Article  Google Scholar 

  • Lockhart MM, Wirrig EE, Phelps AL, Ghatnekar AV, Barth JL, Norris RA, Wessels A (2013) Mef2c regulates transcription of the extracellular matrix protein cartilage link protein 1 in the developing murine heart. PLoS One 8:e57073

    Article  CAS  Google Scholar 

  • Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta N, Steer BM, Ingram AJ, Gupta M, Al-Omran M, Teoh H, Marsden PA, Verma S (2012) MicroRNA-145 targeted therapy reduces atherosclerosis. Circulation 126:S81–S90

    Article  CAS  Google Scholar 

  • Lv Y, Lei Y, Hu Y, Ding W, Zhang C, Fang C (2015) miR-448 negatively regulates ovarian cancer cell growth and metastasis by targeting CXCL12. Clin Trans Oncol 17:903–909

    Article  CAS  Google Scholar 

  • Ohdaira H, Sekiguchi M, Miyata K, Yoshida K (2012) MicroRNA-494 suppresses cell proliferation and induces senescence in A549 lung cancer cells. Cell Prolif 45:32–38

    Article  CAS  Google Scholar 

  • Pirillo A, Norata GD, Catapano AL (2013) LOX-1, OxLDL, and atherosclerosis. Mediat Inflamm 2013:152786

    Article  Google Scholar 

  • Qin B, Xiao B, Liang D, Li Y, Jiang T, Yang H (2012) MicroRNA let-7c inhibits Bcl-xl expression and regulates ox-LDL-induced endothelial apoptosis. BMB Rep 45:464–469

    Article  CAS  Google Scholar 

  • Sturtzel C, Testori J, Schweighofer B, Bilban M, Hofer E (2014) The transcription factor MEF2C negatively controls angiogenic sprouting of endothelial cells depending on oxygen. PLoS One 9:e101521

    Article  Google Scholar 

  • Sun Y, Chen D, Cao L, Zhang R, Zhou J, Chen H, Li Y, Li M, Cao J, Wang Z (2013) MiR-490-3p modulates the proliferation of vascular smooth muscle cells induced by ox-LDL through targeting PAPP-A. Cardiovasc Res 100:272–279

    Article  CAS  Google Scholar 

  • Villeneuve LM, Kato M, Reddy MA, Wang M, Lanting L, Natarajan R (2010) Enhanced levels of microRNA-125b in vascular smooth muscle cells of diabetic db/db mice lead to increased inflammatory gene expression by targeting the histone methyltransferase Suv39h1. Diabetes 59:2904–2915

    Article  CAS  Google Scholar 

  • Xu Z, Gong J, Maiti D, Vong L, Wu L, Schwarz JJ, Duh EJ (2012) MEF2C ablation in endothelial cells reduces retinal vessel loss and suppresses pathologic retinal neovascularization in oxygen-induced retinopathy. Am J Pathol 180:2548–2560

    Article  CAS  Google Scholar 

  • Xu Z, Han Y, Liu J, Jiang F, Hu H, Wang Y, Liu Q, Gong Y, Li X (2015a) MiR-135b-5p and MiR-499a-3p promote cell proliferation and migration in atherosclerosis by directly targeting MEF2C. Sci Rep 5:12276

    Article  CAS  Google Scholar 

  • Xu Z, Yoshida T, Wu L, Maiti D, Cebotaru L, Duh EJ (2015b) Transcription factor MEF2C suppresses endothelial cell inflammation via regulation of NF-kappaB and KLF2. J Cell Physiol 230:1310–1320

    Article  CAS  Google Scholar 

  • Yu X, Li Z, Shen J, Wu WK, Liang J, Weng X, Qiu G (2013a) MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration. PLoS One 8:e83080

    Article  Google Scholar 

  • Yu X, Zhang X, Bi T, Ding Y, Zhao J, Wang C, Jia T, Han D, Guo G, Wang B, Jiang J, Cui S (2013b) MiRNA expression signature for potentially predicting the prognosis of ovarian serous carcinoma. Tum Biol 34:3501–3508

    Article  CAS  Google Scholar 

  • Yu X, Li Z (2014) MicroRNAs regulate vascular smooth muscle cell functions in atherosclerosis (review). Int J Mol Med 34:923–933

    Article  CAS  Google Scholar 

  • Yu X, Li Z (2015) The role of microRNAs expression in laryngeal cancer. Oncotarget 6:23297–23305

    Article  Google Scholar 

  • Yu X, Li Z, Chen G, Wu WK (2015a) MicroRNA-10b induces vascular muscle cell proliferation through Akt pathway by targeting TIP30. Curr Vasc Pharmacol 13:679–686

    Article  CAS  Google Scholar 

  • Yu X, Li Z, Yu J, Chan MT, Wu WK (2015b) MicroRNAs predict and modulate responses to chemotherapy in colorectal cancer. Cell Prolif 48:503–510

    Article  CAS  Google Scholar 

  • Zhang CF, Kang K, Li XM, Xie BD (2015) MicroRNA-136 promotes vascular muscle cell proliferation through the ERK1/2 pathway by targeting PPP2R2A in atherosclerosis. Curr Vasc Pharmacol 13:405–412

    Article  CAS  Google Scholar 

  • Zhu H, Zhou X, Ma C, Chang H, Li H, Liu F, Lu J (2015) Low expression of miR-448 induces EMT and promotes invasion by regulating ROCK2 in hepatocellular carcinoma. Cell Physiol Biochem 36:487–498

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants from the Research project of science and technology of Heilongjiang Province (Grant Number: 11531174) and Research project of Health Department of Heilongjiang Province (Grant number: 2007164).

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Authors and Affiliations

  1. Department of Cardiovascular, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China

    Ruihong Zhang, Xiaojian Hong & Weimin Li

  2. Department of Emergency, the First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China

    Li Sui

  3. Department of Cardiovascular, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China

    Mao Yang

Authors
  1. Ruihong Zhang
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  2. Li Sui
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  3. Xiaojian Hong
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  4. Mao Yang
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  5. Weimin Li
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Contributions

Ruihong Zhang, Li Sui, Xiaojian Hong, Mao Yang, and Weimin Li carried out the molecular studies, participated in the sequence alignment, and drafted the manuscript. Ruihong Zhang carried out the immunoassays. Li Sui participated in the sequence alignment. Mao Yang and Weimin Li participated in the design of the study and performed the statistical analysis. Xiaojian Hong and Weimin Li conceived of the study, and participated in its design and coordination and helped draft the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Weimin Li.

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The authors declare that they have no competing interests.

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Responsible editor: Philippe Garrigues

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Zhang, R., Sui, L., Hong, X. et al. MiR-448 promotes vascular smooth muscle cell proliferation and migration in through directly targeting MEF2C. Environ Sci Pollut Res 24, 22294–22300 (2017). https://doi.org/10.1007/s11356-017-9771-1

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  • DOI: https://doi.org/10.1007/s11356-017-9771-1

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