TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000543185
  • Gene Name:HDAC4
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB00188
  • Drug Name:Bortezomib
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:multiple myeloma
  • Tissue:cell lines U266, NCI-H929, and RPMI-8226 w

Other information

  • Title:MIR145-3p promotes autophagy and enhances bortezomib sensitivity in multiple myeloma by targeting HDAC4
  • Journal:Autophagy
  • Published:2019
  • PubMed ID:31242129
  • Abstract:Multiple myeloma (MM) is an incurable plasma cell malignancy with poor survival. Autophagy, a stress-responsive catabolic process mediated by lysosomal activity, plays a crucial role in the pathophysiology of MM. Growing evidence has indicated that dysregulated microRNAs (miRNAs) are associated with the aberrant autophagy in various human cancers. However, to date, few miRNAs have been reported to directly modulate autophagy in the pathobiology of MM. In this study, we investigated the role of MIR145-3p (microRNA 145-3p) in MM, with focus on cellular processes autophagy and cell death. Our results provided evidence that downregulation of MIR145-3p expression was associated with disease progression in human MM. MIR145-3p triggered autophagic flux through direct targeting of HDAC4 (histone deacetylase 4) in MM cells, leading to enhanced apoptosis. Silencing HDAC4 recapitulated the effects of MIR145-3p, whereas enforced expression of HDAC4 abrogated the effects of MIR145-3p. Furthermore, we showed that suppression of HDAC4 by MIR145-3p resulted in upregulation of the pro-apoptotic protein BCL2L11 and caused MTORC1 inactivation, which in turn led to enhanced autophagy and cell death. Importantly, we demonstrated that MIR145-3p mimic could potentiate the anti-MM activity of bortezomib in both in vitro and in vivo experiments. Overall, our findings indicate that MIR145-3p exerted a tumor suppression function in MM by inducing autophagic cell death and suggest that MIR145-3p-based targeted therapy would represent a novel strategy for MM treatment.
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