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PSMD2 regulates breast cancer cell proliferation and cell cycle progression by modulating p21 and p27 proteasomal

Yunhai Li1, Jing Huang2, Beilei Zeng3

  • 1Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Cancer Letters
|May 20, 2018
PubMed

Insights

PSMD2 is upregulated in breast cancer, promoting tumor growth by degrading cell cycle inhibitors p21 and p27. Inhibiting PSMD2 with small interfering RNA suppressed tumor growth, suggesting PSMD2 as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Alterations in the ubiquitin-proteasome system (UPS) are linked to human cancers.
  • The role of specific UPS proteins in breast cancer progression requires further elucidation.

Purpose of the Study:

  • To investigate the role of PSMD2, a UPS-associated gene, in breast cancer.
  • To explore PSMD2 as a potential therapeutic target for breast cancer.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) HiSeq data for 797 UPS-related genes.
  • PSMD2 knockdown in vitro and in vivo models.
  • Gene set enrichment analysis.
  • Western blotting and rescue assays.
  • Intratumor injection of PSMD2 small interfering RNA (siRNA).

Main Results:

  • PSMD2 was significantly upregulated in breast cancer, correlating with poor prognosis.
  • Elevated PSMD2 expression was associated with signatures of proliferation, cell cycle progression, and apoptosis.
  • PSMD2 knockdown inhibited proliferation, induced G0/G1 cell cycle arrest, and suppressed tumor growth.
  • PSMD2 interacted with and mediated the degradation of p21 and p27, key cell cycle inhibitors.
  • PSMD2 siRNA treatment delayed xenograft tumor growth and increased p21/p27 levels.

Conclusions:

  • PSMD2 plays a crucial role in promoting breast cancer progression.
  • PSMD2 facilitates cell proliferation and tumor growth by targeting p21 and p27 for degradation.
  • PSMD2 represents a promising therapeutic target for breast cancer treatment.
Keywords:
Breast cancerCell cyclePSMD2Ubiquitin-proteasome systemp21p27

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