TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000263269
  • Gene Name:GRIN2D
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:miR-129-1-3p/Ca2+signalling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB11616
  • Drug Name:Pirarubicin
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:cardiac damage
  • Tissue:tissues

Other information

  • Title:MicroRNA-129-1-3p protects cardiomyocytes from pirarubicin-induced apoptosis by down-regulating the GRIN2D-mediated Ca2+?signalling pathway
  • Journal:Journal of Cellular And Molecular Medicine
  • Published:2020
  • PubMed ID:31957170
  • Abstract:Pirarubicin (THP), an anthracycline anticancer drug, is a first-line therapy for various solid tumours and haematologic malignancies. However, THP can cause dose-dependent cumulative cardiac damage, which limits its therapeutic window. The mechanisms underlying THP cardiotoxicity are not fully understood. We previously showed that MiR-129-1-3p, a potential biomarker of cardiovascular disease, was down-regulated in a rat model of THP-induced cardiac injury. In this study, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses to determine the pathways affected by miR-129-1-3p expression. The results linked miR-129-1-3p to the Ca2+signalling pathway. TargetScan database screening identified a tentative miR-129-1-3p-binding site at the 3＇-UTR of GRIN2D, a subunit of the N-methyl-D-aspartate receptor calcium channel. A luciferase reporter assay confirmed that miR-129-1-3p directly regulates GRIN2D. In H9C2 (rat) and HL-1 (mouse) cardiomyocytes, THP caused oxidative stress, calcium overload and apoptotic cell death. These THP-induced changes were ameliorated by miR-129-1-3p overexpression, but exacerbated by miR-129-1-3p knock-down. In addition, miR-129-1-3p overexpression in cardiomyocytes prevented THP-induced changes in the expression of proteins that are either key components of Ca2+signalling or important regulators of intracellular calcium trafficking/balance in cardiomyocytes including GRIN2D, CALM1, CaMKⅡδ, RyR2-pS2814, SERCA2a and NCX1. Together, these bioinformatics and cell-based experiments indicate that miR-129-1-3p protects against THP-induced cardiomyocyte apoptosis by down-regulating the GRIN2D-mediated Ca2+pathway. Our results reveal a novel mechanism underlying the pathogenesis of THP-induced cardiotoxicity. The miR-129-1-3p/Ca2+signalling pathway could serve as a target for the development of new cardioprotective agents to control THP-induced cardiotoxicity.
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