TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000397062
  • Gene Name:NFE2L2
  • 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:hepatocellular carcinoma
  • Tissue:HepG2/DDP

Other information

  • Title:Enhancer-bound Nrf2 licenses HIF-1α transcription under hypoxia to promote cisplatin resistance in hepatocellular carcinoma cells.
  • Journal:Aging (Albany NY)
  • Published:2020
  • PubMed ID:33290263
  • Abstract:Tumor microenvironment is hypoxic, which can cause resistance to chemotherapy, but the detailed mechanisms remain elusive. Here we find that mild hypoxia (5% O2) further increases cisplatin resistance in the already resistant HepG2/DDP but not the sensitive HepG2 cells. We find that Nrf2 is responsible for cisplatin resistance under hypoxia, as Nrf2 knockdown sensitizes HepG2/DDP cells while Nrf2 hyper-activation (though KEAP1 knockdown) increases resistance of HepG2 cells to cisplatin. Nrf2 binds to an enhancer element in the upstream of HIF-1α gene independently of hypoxia, promoting HIF-1α mRNA synthesis under hypoxic condition. As a result, Nrf2-dependent transcription counteracts HIF-1α degradation under mild hypoxia condition, leading to preferential cisplatin-resistance in HepG2/DDP cells. Our data suggest that Nrf2 regulation of HIF-1α could be an important mechanism for chemotherapy resistance in vivo.
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