MiR-149 attenuates the proliferation and migration of TGF-β1-induced airway smooth muscle cells by targeting TRPM7 and affecting downstream MAPK signal pathway

Acta Biochim Pol. 2020 Dec 7;67(4):453-460. doi: 10.18388/abp.2020_5417.

Abstract

Asthma is considered as a general term for various chronic inflammatory diseases of the respiratory tract. Growing evidences have supported that microRNAs were involved in mediating cell proliferation, migration, and other cellular functions. MiR-149 has been found to take part in the development of various cancers. However, whether miR-149 participated in the proliferation and migration of transforming growth factor beta 1 (TGF-β1)-induced airway smooth muscle cells was still unknown. In this study, the expression level of miR-149 in human airway smooth muscle cells (ASMCs) was decreased after TGF-β1 treatment in vitro. Additionally, the over-expression of miR-149 obviously suppressed proliferation and migration in human ASMCs. Besides, we found that overexpression of miR-149 could inhibit the expression of transient receptor potential melastatin 7 (TRPM7) both in protein and gene levels. Furthermore, we demonstrated that miR-149 could inhibit the cell proliferation and migration in human ASMCs by targeting TRPM7 through modulating mitogen-activated protein kinases (MAPKs) signaling pathway. Taken together, we strongly supported that miR-149 might be a key inhibitor of asthma by targeting TRMP7. Therefore, our finding suggests a promising biomarker for the development of further targeted therapies for asthma.

MeSH terms

  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Base Pairing
  • Base Sequence
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / metabolism
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Respiratory System / cytology
  • Respiratory System / drug effects
  • Respiratory System / metabolism
  • Signal Transduction / genetics*
  • TRPM Cation Channels / genetics*
  • TRPM Cation Channels / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta1 / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antagomirs
  • MIRN149 microRNA, human
  • MicroRNAs
  • Oligoribonucleotides
  • TGFB1 protein, human
  • TRPM Cation Channels
  • Transforming Growth Factor beta1
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • TRPM7 protein, human
  • MAPK1 protein, human
  • MAPK3 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4