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PSMD4 drives progression of hepatocellular carcinoma via Akt/COX2 pathway and p53 inhibition

Jiamin Zhang1,2, Shu Fang1,2, Fanghao Rong1,2

  • 1Department of Human Anatomy, Hebei Medical University, Shijiazhuang, Hebei, China.

Human Cell
|June 19, 2023
PubMed

Insights

Proteasome 26S Subunit Ubiquitin Receptor, Non-ATPase 4 (PSMD4) drives hepatocellular carcinoma (HCC) growth by activating the COX2 pathway and downregulating p53. Targeting PSMD4 offers a potential therapeutic strategy for HCC patients.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • The ubiquitin-dependent proteolytic pathway regulates critical cellular processes.
  • Proteasome 26S Subunit Ubiquitin Receptor, Non-ATPase 4 (PSMD4) is upregulated in hepatocellular carcinoma (HCC) and linked to poor prognosis.

Purpose of the Study:

  • To investigate the role of PSMD4 in HCC development and its underlying molecular mechanisms.
  • To explore potential therapeutic strategies targeting PSMD4 in HCC.

Main Methods:

  • Transcriptome sequencing of HCC and non-tumor tissues from The Cancer Genome Atlas (TCGA).
  • In vivo studies using a mouse xenograft model with PSMD4-deficient HCC cells.
  • Analysis of PSMD4's association with signaling pathways, including Akt/GSK-3β/cyclooxygenase2 (COX2) and p53.

Main Results:

  • High PSMD4 expression was confirmed in HCC tissues.
  • PSMD4 loss significantly suppressed tumor growth in a mouse xenograft model.
  • PSMD4 promotes HCC cell growth via COX2 activation and p53 downregulation, with its VWA+UIM1/2 domain maintaining p53 transcription.

Conclusions:

  • PSMD4 is a key driver of HCC progression, mediating tumor growth through COX2 upregulation and p53 inhibition.
  • Targeting PSMD4 and its downstream pathways presents a promising therapeutic avenue for HCC.
Keywords:
COX2HCCPSMD4Tumor growthp53

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