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Updated: Jan 7, 2026

The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers

Published on: January 22, 2013

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Targeting USP28 inhibits clear cell renal cell carcinoma growth

Ying Ren1, Yunfang Yang2, Xiaodan Zhu3

  • 1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.

Cellular Signalling
|December 28, 2025
PubMed

Insights

Researchers found that USP28 stabilizes c-Myc protein in clear cell renal cell carcinoma (ccRCC). Inhibiting USP28 reduces c-Myc, slows ccRCC cell growth, and shrinks tumors, offering a new therapeutic target for this kidney cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and lacks effective targeted treatments.
  • Overexpression of c-Myc is common in ccRCC, but the mechanisms controlling its stability are unclear.
  • Understanding c-Myc regulation is crucial for developing novel ccRCC therapies.

Purpose of the Study:

  • To identify key regulators of c-Myc protein stability in ccRCC.
  • To investigate the therapeutic potential of targeting c-Myc stabilization pathways in ccRCC.

Main Methods:

  • Investigated the interaction between USP28 and c-Myc in ccRCC cells.
  • Assessed the role of USP28 in c-Myc deubiquitination and proteasomal degradation.
  • Utilized genetic and pharmacological inhibition of USP28 in vitro and in vivo ccRCC models.
  • Correlated c-Myc expression levels with sensitivity to USP28 inhibition.

Main Results:

  • USP28 deubiquitinates c-Myc by removing K48-linked chains, preventing its degradation.
  • USP28 inhibition significantly reduces c-Myc levels, impairs ccRCC cell proliferation, and suppresses tumor growth.
  • ccRCC tumors with high c-Myc expression are more sensitive to USP28 inhibition.

Conclusions:

  • USP28 is a critical regulator of c-Myc protein stability in ccRCC.
  • Targeting USP28 represents a promising therapeutic strategy for ccRCC, particularly in tumors with high c-Myc.
  • This study highlights the USP28-c-Myc axis as a potential therapeutic target for kidney cancer.
Keywords:
AZ1C-MycUSP28Ubiquitin-proteasome systemccRCC

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