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Navigating the Mass Spectrometry-Based Proteomic Data Using Free Computational Tools
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Published on: August 19, 2025

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Proteome Analysis of USP7 Substrates Revealed Its Role in Melanoma Through PI3K/Akt/FOXO and AMPK Pathways

Lanyang Gao1,2, Danli Zhu1, Qin Wang1

  • 1Sichuan Provincial Center for Gynaecology and Breast Disease, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Frontiers in Oncology
|April 19, 2021
PubMed

Insights

Ubiquitin-specific protease 7 (USP7) drives melanoma progression by impacting key signaling pathways. Inhibiting USP7 shows promise as an anticancer strategy for melanoma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme implicated in tumor progression.
  • The specific role of USP7 in melanoma pathogenesis is not well understood.
  • USP7 is recognized as a potential therapeutic target for various cancers.

Purpose of the Study:

  • To investigate the functional role of USP7 in melanoma.
  • To identify molecular pathways regulated by USP7 in melanoma cells.
  • To evaluate USP7 as a potential therapeutic target for melanoma.

Main Methods:

  • Tissue microarray analysis to assess USP7 expression in human melanoma.
  • TMT-based quantitative proteomic analysis of A375 melanoma cells with USP7 knockdown via siRNA.
  • CRISPR-Cas9 gene editing to create USP7 knockout melanoma cells.
  • In vitro and in vivo assays to assess cell proliferation.

Main Results:

  • USP7 is overexpressed in human melanoma.
  • USP7 knockdown or knockout significantly impacts cell proliferation in vitro and in vivo.
  • USP7 regulates the phosphatidylinositol-3-kinases/Akt (PI3K-Akt), forkhead box O (FOXO), and AMP-activated protein kinase (AMPK) signaling pathways.
  • Inhibition of USP7 alters the expression of specific proteins including PRKAB1, CASP7, PPP2R3A, ATP6V0C, and PEX11B.

Conclusions:

  • USP7 plays a critical role in melanoma progression.
  • USP7 regulates melanoma cell proliferation through PI3K/Akt/FOXO and AMPK signaling.
  • USP7 is a promising therapeutic target for melanoma treatment.
Keywords:
PI3K/Akt/FOXO pathwaysUSP7deubiquitinating enzymemelanomaquantitative proteomics

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