Skip to main content
Log in

Identification of the microRNA Expression Profile in the Regenerative Neonatal Mouse Heart by Deep Sequencing

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that are involved in key biological processes, including development, differentiation, and regeneration. The global miRNA expression profile that regulates the regenerative potential of the neonatal mouse heart has not been reported. We performed deep sequencing to determine the genome-wide miRNA expression profile of the neonatal mouse heart at three key ages (1, 6, and 7 days). The miRNAs at least 1.4-fold differentially expressed between the three time points were selected for further analysis. Two miRNAs (mmu-miR-22-5p and mmu-miR-338-3p) were significantly upregulated, and nine miRNAs (mmu-miR-324-5p, mmu-miR-337-5p, mmu-miR-339-5p, mmu-miR-365-1-5p, mmu-miR-500-3p, mmu-miR-505-5p, mmu-miR-542-5p, mmu-miR-668-3p, and mmu-miR-92a-1-5p) were significantly downregulated in cardiac tissue of 7-day-old mice compared to 1- and 6-day-old mice. The expression patterns of five significantly different miRNAs were verified by quantitative real-time PCR. Furthermore, the potential targets of these putative miRNAs were suggested using miRNA target prediction tools. The candidate target genes are involved in the myocardial regenerative process, with a prominent role for the Notch signaling pathway. Our study provides a valuable resource for future investigation of the biological function of miRNAs in heart regeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bartel, D. P. (2009). MicroRNAs: Target recognition and regulatory functions. Cell, 136, 215–233.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Lagos-Quintana, M., Rauhut, R., Lendeckel, W., & Tuschl, T. (2001). Identification of novel genes coding for small expressed RNAs. Science, 294, 853–858.

    Article  CAS  PubMed  Google Scholar 

  3. Mendell, J. T. (2005). MicroRNAs: Critical regulators of development, cellular physiology and malignancy. Cell Cycle, 4, 1179–1184.

    Article  CAS  PubMed  Google Scholar 

  4. Yin, V. P., Lepilina, A., Smith, A., & Poss, K. D. (2012). Regulation of zebrafish heart regeneration by miR-133. Development Biology, 365(2), 319–327.

    Article  CAS  Google Scholar 

  5. Poss, K. D., Wilson, L. G., & Keating, M. T. (2002). Heart regeneration in zebrafish. Science, 298(5601), 2188–2190.

    Article  CAS  PubMed  Google Scholar 

  6. Oberpriller, J. O., & Oberpriller, J. C. (1974). Response of the adult newt ventricle to injury. Journal of Experimental Zoology, 187(2), 249–259.

    Article  CAS  PubMed  Google Scholar 

  7. Porrello, E. R., Mahmoud, A. I., Simpson, E., Hill, J. A., Richardson, J. A., Olson, E. N., et al. (2011). Transient regenerative potential of the neonatal mouse heart. Science, 331(6020), 1078–1080.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Lau, N. C., Lim, L. P., Weinstein, E. G., & Bartel, D. P. (2001). An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science, 294, 858–862.

    Article  CAS  PubMed  Google Scholar 

  9. Jopling, C., Sleep, E., Raya, M., Martí, M., Raya, A., & Belmonte, J. C. I. (2010). Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature, 464(7288), 606–609.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Thatcher, E. J., & Patton, J. G. (2010). Small RNAs have a big impact on regeneration. RNA Biology, 7(3), 333–338.

    Article  CAS  PubMed  Google Scholar 

  11. Liu, N., & Olson, E. N. (2010). MicroRNA regulatory networks in cardiovascular development. Developmental Cell, 18(4), 510–525.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Kuhl, C., Atzberger, A., Iborra, F., Nieswandt, B., Porcher, C., & Vyas, P. (2005). GATA1-mediated megakaryocyte differentiation and growth control can be uncoupled and mapped to different domains in GATA1. Molecular and Cellular Biology, 25(19), 8592–8606.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Caprioli, A., Koyano-Nakagawa, N., Iacovino, M., Shi, X., Ferdous, A., Harvey, R. P., et al. (2011). Nk2–5 represses Gata1 gene expression and modulates the cellular fate of cardiac progenitors during embryogenesis. Circulation, 123(15), 1633–1641.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Fu, X., Tan, D., Hou, Z., Hu, Z., Liu, G., Ouyang, Y., et al. (2012). The effect of miR-338-3p on HBx deletion-mutant (HBx-d382) mediated liver-cell proliferation through cyclinD1 regulation. PLoS One, 7(8), e43204.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Takeuchi, J. K., & Bruneau, B. G. (2009). Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature, 459(7247), 708–711.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Ieda, M., Fu, J. D., Delgado-Olguin, P., Vedantham, V., Hayashi, Y., Bruneau, B. G., et al. (2010). Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell, 142(3), 375–386.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Malekar, P., Hagenmueller, M., Anyanwu, A., Buss, S., Streit, M. R., Weiss, C. S., et al. (2010). Wnt signaling is critical for maladaptive cardiac hypertrophy and accelerates myocardial remodeling. Hypertension, 55, 939–945.

    Article  CAS  PubMed  Google Scholar 

  18. Kemi, O. J., Ceci, M., Wisloff, U., Grimaldi, S., Gallo, P., Smith, G. L., et al. (2008). Activation or inactivation of cardiac Akt/mTOR signaling diverges physiological from pathological hypertrophy. Journal of Cellular Physiology, 214, 316–321.

    Article  CAS  PubMed  Google Scholar 

  19. Stoick-Cooper, C. L., Weidinger, G., Riehle, K. J., Hubbert, C., Major, M. B., Fausto, N., et al. (2007). Distinct Wnt signaling pathways have opposing roles in appendage regeneration. Development, 134(3), 479–489.

    Article  CAS  PubMed  Google Scholar 

  20. Falix, F. A., Aronson, D. C., Lamers, W. H., & Gaemers, I. C. (2012). Possible roles of DLK1 in the notch pathway during development and disease. Biochimica et Biophysica Acta, 1822(6), 988–995.

    Article  CAS  PubMed  Google Scholar 

  21. Xu, K., Usary, J., Kousis, P. C., Prat, A., Wang, D. Y., Adams, J. R., et al. (2012). Lunatic fringe deficiency cooperates with the Met/Caveolin gene amplicon to induce basal-like breast cancer. Cancer Cell, 21(5), 626–641.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. De Lange, R. P., Burr, K., Clark, J. S., Negrin, C. D., Brosnan, M. J., St Clair, D. M., et al. (2001). Mapping and sequencing rat dishevelled-1: A candidate gene for cerebral ischaemic insult in a rat model of stroke. Neurogenetics, 3(2), 99–106.

    Article  PubMed  Google Scholar 

  23. Raya, A., Koth, C. M., Büscher, D., Kawakami, Y., Itoh, T., Raya, R. M., et al. (2003). Activation of notch signaling pathway precedes heart regeneration in zebrafish. Proc Natl Acad Sci USA, 30(100 Suppl 1), 11889–11895.

    Article  Google Scholar 

Download references

Acknowledgments

This study was supported by Grants from the National Natural Science Foundation of China (Nos. 81070138 and 81200126) and the National Natural Science Foundation of Jiangsu Province of China (No. BK2010582).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to C. Zhu or L. M. Qian.

Additional information

Liu HL and Zhu JG contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, H.L., Zhu, J.G., Liu, Y.Q. et al. Identification of the microRNA Expression Profile in the Regenerative Neonatal Mouse Heart by Deep Sequencing. Cell Biochem Biophys 70, 635–642 (2014). https://doi.org/10.1007/s12013-014-9967-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-014-9967-7

Keywords

Navigation