TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000673742
  • Gene Name:CASP8
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:NA
  • Drug Method:NA

Disease basic infommation

  • Disease:breast cancer
  • Tissue:Human TNBC cell lines MDA-MB-436, HCC70, BT-20, and BT549

Other information

  • Title:Knockdown of miR-182 promotes apoptosis via regulating RIP1 deubiquitination in TNF-α-treated triple-negative breast cancercells
  • Journal:Tumor Biol
  • Published:2016
  • PubMed ID:27476169
  • Abstract:Overexpression of microRNA-182 (miR-182) is found in multiple cancers, but the association of miR-182 expression with the sensitivity of triple-negative breast cancer (TNBC) cells to tumor necrosis factor-alpha (TNF-α) remains unknown. In this study, up-regulation of miR-182 was validated in TNBC patients and cell lines. Knockdown of miR-182 was observed to hinder the proliferation of BT-549 cells. More importantly, knockdown of miR-182 significantly promoted the apoptosis induced by TNF-α treatment in BT-549. JC-1 staining and western blot assays revealed that the K63-linked ubiquitin chains on receptor-interacting protein 1 (RIP1) were removed and the outer mitochondrial membrane potential (MMP) and permeability was altered upon combination of TNF-α with anti-miR-182. We then demonstrated that knockdown of miR-182 up-regulated the expression of cylindromatosis (CYLD) deubiquitinase, which promoted the formation of death-inducing signaling complex (DISC) and subsequent caspase-8 activation in TNF-α-treated BT-549 cells. Collectively, the results of the present study improve our understanding of the role of miR-182 in TNBC, knockdown of which facilitates the degradation of ubiquitin chains on RIP1, leading to the caspase-8 activation and apoptosis in TNF-α-treated TNBC cells. This may be valuable for the development of cancer therapy.
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