miR‑149 promotes the myocardial differentiation of mouse bone marrow stem cells by targeting Dab2

  • Authors:
    • Mingjun Lu
    • Lingling Xu
    • Min Wang
    • Tao Guo
    • Fuquan Luo
    • Nan Su
    • Shanghui Yi
    • Tao Chen
  • View Affiliations

  • Published online on: April 19, 2018     https://doi.org/10.3892/mmr.2018.8903
  • Pages: 8502-8509
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

To investigate the role of microRNA (miR)‑149 in the cardiac differentiation of mouse bone marrow mesenchymal stem cells (MSCs) in vitro, MSCs were infected with a lentivirus overexpressing miR‑149 and the effect on cardiac differentiation was determined. The quantitative polymerase chain reaction results demonstrated that miR‑149 promoted the expression of cardiac‑specific markers in MSCs. Western blotting and a luciferase activity assay demonstrated that disabled homolog 2 (Dab2) was a direct target of miR‑149. Dab2 ectopic expression and Wnt/β‑catenin signaling pathway inhibition was able to reverse the increased expression of cardiac‑specific markers induced by miR‑149. In conclusion, miR‑149 was able to target Dab2 and promote the cardiac differentiation of mouse MSCs in vitro, which depended upon the Wnt/β‑catenin signaling pathway.

References

1 

Carvalho E, Verma P, Hourigan K and Banerjee R: Myocardial infarction: Stem cell transplantation for cardiac regeneration. Regen Med. 10:1025–1043. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Cho GS, Fernandez L and Kwon C: Regenerative medicine for the heart: Perspectives on stem-cell therapy. Antioxid Redox Signal. 21:2018–2031. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després JP, Fullerton HJ, Howard VJ, et al: Heart disease and stroke statistics-2015 update: A report from the American Heart Association. Circulation. 131:e29–e322. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Poglajen G and Vrtovec B: Stem cell therapy for chronic heart failure. Curr Opin Cardiol. 30:301–310. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Oliveira MS, Saldanha-Araujo F, Goes AM, Costa FF and de Carvalho JL: Stem cells in cardiovascular diseases: Turning bad days into good ones. Drug Discov Today. 22:1730–1739. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Wegener M, Bader A and Giri S: How to mend a broken heart: Adult and induced pluripotent stem cell therapy for heart repair and regeneration. Drug Discov Today. 20:667–685. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Carvalho PH, Daibert AP, Monteiro BS, Okano BS, Carvalho JL, Cunha DN, Favarato LS, Pereira VG, Augusto LE and Del Carlo RJ: Differentiation of adipose tissue-derived mesenchymal stem cells into cardiomyocytes. Arq Bras Cardiol. 100:82–89. 2013.(In English, Portuguese). View Article : Google Scholar : PubMed/NCBI

8 

Wen Z, Zheng S, Zhou C, Yuan W, Wang J and Wang T: Bone marrow mesenchymal stem cells for post-myocardial infarction cardiac repair: microRNAs as novel regulators. J Cell Mol Med. 16:657–671. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Halleux C, Sottile V, Gasser JA and Seuwen K: Multi-lineage potential of human mesenchymal stem cells following clonal expansion. J Musculoskelet Neuronal Interact. 2:71–76. 2001.PubMed/NCBI

10 

Li J, Zhu K, Wang Y, Zheng J, Guo C, Lai H and Wang C: Combination of IGF-1 gene manipulation and 5-AZA treatment promotes differentiation of mesenchymal stem cells into cardiomyocyte-like cells. Mol Med Rep. 11:815–820. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Wang T, Xu Z, Jiang W and Ma A: Cell-to-cell contact induces mesenchymal stem cell to differentiate into cardiomyocyte and smooth muscle cell. Int J Cardiol. 109:74–81. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Arminán A, Gandía C, Bartual M, García-Verdugo JM, Lledó E, Mirabet V, Llop M, Barea J, Montero JA and Sepúlveda P: Cardiac differentiation is driven by NKX2.5 and GATA4 nuclear translocation in tissue-specific mesenchymal stem cells. Stem Cells Dev. 18:907–918. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Shen X, Pan B, Zhou H, Liu L, Lv T, Zhu J, Huang X and Tian J: Differentiation of mesenchymal stem cells into cardiomyocytes is regulated by miRNA-1-2 via WNT signaling pathway. J Biomed Sci. 24:292017. View Article : Google Scholar : PubMed/NCBI

14 

Rosca AM and Burlacu A: Effect of 5-azacytidine: Evidence for alteration of the multipotent ability of mesenchymal stem cells. Stem Cells Dev. 20:1213–1221. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI

16 

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

17 

Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP and Burge CB: Prediction of mammalian microRNA targets. Cell. 115:787–798. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M and Rajewsky N: Combinatorial microRNA target predictions. Nat Genet. 37:495–500. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Hofsteen P, Robitaille AM, Chapman DP, Moon RT and Murry CE: Quantitative proteomics identify DAB2 as a cardiac developmental regulator that inhibits WNT/β-catenin signaling. Proc Natl Acad Sci USA. 113:1002–1007. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Chen TS, Lai RC, Lee MM, Choo AB, Lee CN and Lim SK: Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids Res. 38:215–224. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Cimpeanu RA, Popescu DM, Burada F, Cucu MG, Gheonea DI, Ioana M and Rogoveanu I: miR-149 rs2292832 C>T polymorphism and risk of gastric cancer. Rom J Morphol Embryol. 58:125–129. 2017.PubMed/NCBI

23 

Ow SH, Chua PJ and Bay BH: miR-149 as a potential molecular target for cancer. Curr Med Chem. Jul 18–2017.(Epub ahead of print).

24 

Alipoor B, Meshkani R, Ghaedi H, Sharifi Z, Panahi G and Golmohammadi T: Association of miR-146a rs2910164 and miR-149 rs2292832 variants with susceptibility to type 2 diabetes. Clin Lab. 62:1553–1561. 2016. View Article : Google Scholar : PubMed/NCBI

25 

An X, Yang Z and An Z: MiR-149 compromises the reactions of liver cells to fatty acid via its polymorphism and increases Non-alcoholic fatty liver disease (NAFLD) risk by targeting methylene tetrahydrofolate reductase (MTHFR). Med Sci Monit. 23:2299–2307. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Du J, Cui C, Zhang S, Yang X and Lou J: Association of MicroRNA-146a and MicroRNA-149 polymorphisms with strokes in asian populations: An updated meta-analysis. Angiology. 68:863–870. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Yu JY, Hu F, Du W, Ma XL and Yuan K: Study of the association between five polymorphisms and risk of hepatocellular carcinoma: A meta-analysis. J Chin Med Assoc. 80:191–203. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Zheng L, Zhuang C, Zhao J and Ming L: Functional miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms and the susceptibility to hepatocellular carcinoma: An updated meta-analysis. Clin Res Hepatol Gastroenterol. 41:664–676. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Kaneko M, Satomi T, Fujiwara S, Uchiyama H, Kusumoto K and Nishimoto T: AT1 receptor blocker azilsartan medoxomil normalizes plasma miR-146a and miR-342-3p in a murine heart failure model. Biomarkers. 22:253–260. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Wu C, Gong Y, Sun A, Zhang Y, Zhang C, Zhang W, Zhao G, Zou Y and Ge J: The human MTHFR rs4846049 polymorphism increases coronary heart disease risk through modifying miRNA binding. Nutr Metab Cardiovasc Dis. 23:693–698. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Finkielstein CV and Capelluto DG: Disabled-2: A modular scaffold protein with multifaceted functions in signaling. Bioessays. 38 Suppl 1:S45–S55. 2016. View Article : Google Scholar : PubMed/NCBI

32 

Adamson SE, Griffiths R, Moravec R, Senthivinayagam S, Montgomery G, Chen W, Han J, Sharma PR, Mullins GR, Gorski SA, et al: Disabled homolog 2 controls macrophage phenotypic polarization and adipose tissue inflammation. J Clin Invest. 126:1311–1322. 2016. View Article : Google Scholar : PubMed/NCBI

33 

Zhang Z, Chen Y, Tang J and Xie X: Frequent loss expression of dab2 and promotor hypermethylation in human cancers: A meta-analysis and systematic review. Pak J Med Sci. 30:432–437. 2014.PubMed/NCBI

34 

Hannigan A, Smith P, Kalna G, Lo Nigro C, Orange C, O'Brien DI, Shah R, Syed N, Spender LC, Herrera B, et al: Epigenetic downregulation of human disabled homolog 2 switches TGF-beta from a tumor suppressor to a tumor promoter. J Clin Invest. 120:2842–2857. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

June 2018
Volume 17 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Lu, M., Xu, L., Wang, M., Guo, T., Luo, F., Su, N. ... Chen, T. (2018). miR‑149 promotes the myocardial differentiation of mouse bone marrow stem cells by targeting Dab2. Molecular Medicine Reports, 17, 8502-8509. https://doi.org/10.3892/mmr.2018.8903
MLA
Lu, M., Xu, L., Wang, M., Guo, T., Luo, F., Su, N., Yi, S., Chen, T."miR‑149 promotes the myocardial differentiation of mouse bone marrow stem cells by targeting Dab2". Molecular Medicine Reports 17.6 (2018): 8502-8509.
Chicago
Lu, M., Xu, L., Wang, M., Guo, T., Luo, F., Su, N., Yi, S., Chen, T."miR‑149 promotes the myocardial differentiation of mouse bone marrow stem cells by targeting Dab2". Molecular Medicine Reports 17, no. 6 (2018): 8502-8509. https://doi.org/10.3892/mmr.2018.8903