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Article Open Access

Downregulation of microRNA‑34b is responsible for the elevation of blood pressure in spontaneously hypertensive rats

  • Authors:
    • Fan Yang
    • Haiyu Li
    • Youyou Du
    • Qiangwei Shi
    • Luosha Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1031-1036
    |
    Published online on: January 16, 2017
       https://doi.org/10.3892/mmr.2017.6122
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Abstract

The present study aimed to identify the microRNA (miRNA) responsible for the development of primary hypertension, and examine the downstream signaling pathway, which mediates the effect of the miRNA. Reverse transcription‑quantitative polymerase chain reaction analysis was performed to identify which miRNA may be involved in the pathogenesis of hypertension. In silico analysis and a luciferase assay were used to validate the target of the selected miRNA, and miRNA mimics and small interfering (si)RNA of the target were transfected into smooth muscle cells to examine its effect on the biological activity of the cells. miR‑34b was found to be upregulated in spontaneously hypertensive rats (SHRs), compared with Wistar Kyoto (WKY) rats. Therefore, the present study used online miRNA target prediction tools to predict the candidate target genes of miR‑34b in the database, and consequently identified cyclin G1 (CCNG1) and cyclin‑dependent kinase 6 (CDK6) as its possible target genes. CDK6 subsequently identified to be the direct target gene of miR‑34b using a luciferase reporter assay in vascular smooth muscle cells (VSMCs). The present study also established the possible negative regulatory association between miR‑34b and CDK6 via investigating the mRNA and protein expression levels of CDK6 and CCNG1 in VSMCs collected from the SHRs and WKY rats, respectively. To investigate the signaling pathways between miR‑34b and CDK6, the mRNA and protein expression levels of CDK6, and the proliferation rates were compared in VSMCs transfected with CDK6 siRNA or miR‑34b mimics, the results of which indicated that the miR‑34b mimics exerted the same effects on the expression of CDK6 and cell proliferation as CDK6 siRNA. The negative regulatory association between miR‑34b and its target, CDK6, was confirmed, which may offer potential as a novel therapeutic target in the treatment of hypertension.
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1 

Owens GK, Kumar MS and Wamhoff BR: Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev. 84:767–801. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Rzucidlo EM: Signaling pathways regulating vascular smooth muscle cell differentiation. Vascular. 17:(Suppl 1). S15–S20. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Moazed D: Small RNAs in transcriptional gene silencing and genome defence. Nature. 457:413–420. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Krol J, Loedige I and Filipowicz W: The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 11:597–610. 2010.PubMed/NCBI

5 

Boettger T, Beetz N, Kostin S, Schneider J, Krüger M, Hein L and Braun T: Acquisition of the contractile phenotype by murine arterial smooth muscle cells depends on the Mir143/145 gene cluster. J Clin Invest. 119:2634–2647. 2009. View Article : Google Scholar : PubMed/NCBI

6 

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.PubMed/NCBI

7 

Xin M, Small EM, Sutherland LB, Qi X, McAnally J, Plato CF, Richardson JA, Bassel-Duby R and Olson EN: MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. Genes Dev. 23:2166–2178. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Deacon DC, Nevis KR, Cashman TJ, Zhou Y, Zhao L, Washko D, Guner-Ataman B, Burns CG and Burns CE: The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis. Development. 137:1887–1896. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Quintavalle M, Elia L, Condorelli G and Courtneidge SA: MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro. J Cell Biol. 189:13–22. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Davis BN, Hilyard AC, Nguyen PH, Lagna G and Hata A: Induction of microRNA-221 by platelet-derived growth factor signaling is critical for modulation of vascular smooth muscle phenotype. J Biol Chem. 284:3728–3738. 2009. View Article : Google Scholar : PubMed/NCBI

11 

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

12 

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

13 

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

14 

Elia L, Quintavalle M, Zhang J, Contu R, Cossu L, Latronico MV, Peterson KL, Indolfi C, Catalucci D, Chen J, et al: The knockout of miR-143 and −145 alters smooth muscle cell maintenance and vascular homeostasis in mice: Correlates with human disease. Cell Death Differ. 16:1590–1598. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Zhang C: MicroRNA-145 in vascular smooth muscle cell biology: A new therapeutic target for vascular disease. Cell Cycle. 8:3469–3473. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Yu ML, Wang JF, Wang GK, You XH, Zhao XX, Jing Q and Qin YW: Vascular smooth muscle cell proliferation is influenced by let-7d microRNA and its interaction with KRAS. Circ J. 75:703–709. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Louis WJ and Howes LG: Genealogy of the spontaneously hypertensive rat and Wistar-Kyoto rat strains: Implications for studies of inherited hypertension. J Cardiovasc Pharmacol. 16:(Suppl 7). S1–S5. 1990. View Article : Google Scholar : PubMed/NCBI

18 

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

19 

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

20 

Xie C, Huang H, Sun X, Guo Y, Hamblin M, Ritchie RP, Garcia-Barrio MT, Zhang J and Chen YE: MicroRNA-1 regulates smooth muscle cell differentiation by repressing Kruppel-like factor 4. Stem Cells Dev. 20:205–210. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Villeneuve LM, Kato M, Reddy MA, Wang M, Lanting L and Natarajan R: 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. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Small EM, Sutherland LB, Rajagopalan KN, Wang S and Olson EN: MicroRNA-218 regulates vascular patterning by modulation of Slit-Robo signaling. Circ Res. 107:1336–1344. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, Weber M, Hamm CW, Röxe T, Müller-Ardogan M, et al: Circulating microRNAs in patients with coronary artery disease. Circ Res. 107:677–684. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Hermeking H: The miR-34 family in cancer and apoptosis. Cell Death Differ. 17:193–199. 2010. View Article : Google Scholar : PubMed/NCBI

25 

He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, Xue W, Zender L, Magnus J, Ridzon D, et al: A microRNA component of the p53 tumour suppressor network. Nature. 447:1130–1134. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Choi YJ, Lin CP, Ho JJ, He X, Okada N, Bu P, Zhong Y, Kim SY, Bennett MJ, Chen C, et al: miR-34 miRNAs provide a barrier for somatic cell reprogramming. Nat Cell Biol. 13:1353–1360. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Bouhallier F, Allioli N, Lavial F, Chalmel F, Perrard MH, Durand P, Samarut J, Pain B and Rouault JP: Role of miR-34c microRNA in the late steps of spermatogenesis. RNA. 16:720–731. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Liu WM, Pang RT, Chiu PC, Wong BP, Lao K, Lee KF and Yeung WS: Sperm-borne microRNA-34c is required for the first cleavage division in mouse. Proc Natl Acad Sci USA. 109:490–494. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Haramati S, Navon I, Issler O, Ezra-Nevo G, Gil S, Zwang R, Hornstein E and Chen A: MicroRNA as repressors of stress-induced anxiety: The case of amygdalar miR-34. J Neurosci. 31:14191–14203. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Aranha MM, Santos DM, Solá S, Steer CJ and Rodrigues CM: miR-34a regulates mouse neural stem cell differentiation. PLoS One. 6:e213962011. View Article : Google Scholar : PubMed/NCBI

31 

Guan H, Zhu L, Fu M, Yang D, Tian S, Guo Y, Cui C, Wang L and Jiang H: 3,3′Diindolylmethane suppresses vascular smooth muscle cell phenotypic modulation and inhibits neointima formation after carotid injury. PLoS One. 7:e349572012. View Article : Google Scholar : PubMed/NCBI

32 

Hotchkiss A, Robinson J, MacLean J, Feridooni T, Wafa K and Pasumarthi KB: Role of D-type cyclins in heart development and disease. Can J Physiol Pharmacol. 90:1197–1207. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang F, Li H, Du Y, Shi Q and Zhao L: Downregulation of microRNA‑34b is responsible for the elevation of blood pressure in spontaneously hypertensive rats. Mol Med Rep 15: 1031-1036, 2017.
APA
Yang, F., Li, H., Du, Y., Shi, Q., & Zhao, L. (2017). Downregulation of microRNA‑34b is responsible for the elevation of blood pressure in spontaneously hypertensive rats. Molecular Medicine Reports, 15, 1031-1036. https://doi.org/10.3892/mmr.2017.6122
MLA
Yang, F., Li, H., Du, Y., Shi, Q., Zhao, L."Downregulation of microRNA‑34b is responsible for the elevation of blood pressure in spontaneously hypertensive rats". Molecular Medicine Reports 15.3 (2017): 1031-1036.
Chicago
Yang, F., Li, H., Du, Y., Shi, Q., Zhao, L."Downregulation of microRNA‑34b is responsible for the elevation of blood pressure in spontaneously hypertensive rats". Molecular Medicine Reports 15, no. 3 (2017): 1031-1036. https://doi.org/10.3892/mmr.2017.6122
Copy and paste a formatted citation
x
Spandidos Publications style
Yang F, Li H, Du Y, Shi Q and Zhao L: Downregulation of microRNA‑34b is responsible for the elevation of blood pressure in spontaneously hypertensive rats. Mol Med Rep 15: 1031-1036, 2017.
APA
Yang, F., Li, H., Du, Y., Shi, Q., & Zhao, L. (2017). Downregulation of microRNA‑34b is responsible for the elevation of blood pressure in spontaneously hypertensive rats. Molecular Medicine Reports, 15, 1031-1036. https://doi.org/10.3892/mmr.2017.6122
MLA
Yang, F., Li, H., Du, Y., Shi, Q., Zhao, L."Downregulation of microRNA‑34b is responsible for the elevation of blood pressure in spontaneously hypertensive rats". Molecular Medicine Reports 15.3 (2017): 1031-1036.
Chicago
Yang, F., Li, H., Du, Y., Shi, Q., Zhao, L."Downregulation of microRNA‑34b is responsible for the elevation of blood pressure in spontaneously hypertensive rats". Molecular Medicine Reports 15, no. 3 (2017): 1031-1036. https://doi.org/10.3892/mmr.2017.6122
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