MAPK1 up-regulates the expression of MALAT1 to promote the proliferation of cardiomyocytes through PI3K/AKT signaling pathway

Int J Clin Exp Pathol. 2015 Dec 1;8(12):15947-53. eCollection 2015.

Abstract

The previous studies identify mammalian heart is terminal differentiation organs without regenerative capacity. Recently, there is some evidence point that cardiomyocytes are not terminally differentiated cells and cell proliferation may be stimulated in the pathologic heart. The aim of this study is to discover the possible mechanism which involved in cardiomyocytes proliferation process. In this study, the proliferation assay and cell cycle assay showed the proliferation of cardiomyocytes was inhibited when the cells treated with MAPK1 inhibitor. Moreover, the bioinformatics analysis revealed MAPK1 was positively correlated with MALAT1. Meanwhile, the expression of MALAT1 in H9C2 cells with the treatment of MAPK1 siRNA was obvious lower than scramble siRNA treated group. Finally further study suggested H9C2 cells treated with Wortmannin in combination with LY294002 (PI3K/AKT signaling pathway inhibitor), the expression of MALAT1 was dramatically decreased. These results indicated that MAPK1 was able to increase the proliferation of cardiomyocytes via up-regulating the expression of MALAT1 through PI3K/AKT signaling pathway.

Keywords: Cardiomyocytes; MALAT1; MAPK1; proliferation.

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Line
  • Cell Proliferation* / drug effects
  • Computational Biology
  • Dose-Response Relationship, Drug
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / enzymology*
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Rats
  • Signal Transduction* / drug effects
  • Time Factors
  • Transfection
  • Up-Regulation

Substances

  • MALAT1 long noncoding RNA, rat
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • RNA, Long Noncoding
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • Mapk1 protein, rat
  • Mitogen-Activated Protein Kinase 1