USP5 promotes tumorigenesis by activating Hedgehog/Gli1 signaling pathway in osteosarcoma

Qing Wu1, Rui Liu2,3, Yuting Yang1

  • 1Department of Orthopedics, The Second Affiliated Hospital of Nanchang University Nanchang 330006, Jiangxi, China.

Insights

Ubiquitin-specific peptidase 5 (USP5) promotes osteosarcoma (OS) progression by activating the hedgehog (Hh) signaling pathway. Elevated USP5 levels correlate with poor prognosis, suggesting USP5 as a potential therapeutic target for OS.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein ubiquitination is crucial in cancer development.
  • Deubiquitinating enzymes (DUBs) are emerging cancer therapeutic targets.
  • Ubiquitin-specific peptidase 5 (USP5) is implicated in various cancers, but its role in osteosarcoma (OS) is unknown.

Purpose of the Study:

  • To investigate the clinical significance and biological function of USP5 in osteosarcoma.
  • To elucidate the mechanism by which USP5 influences OS progression.

Main Methods:

  • Analysis of USP5 expression in OS tissues and patient data.
  • In vitro cell culture experiments and in vivo animal tumor models.
  • Investigation of USP5's effect on the hedgehog (Hh) signaling pathway and Gli1 stability.

Main Results:

  • USP5 expression is elevated in OS tissues and associated with increased mortality and malignancy.
  • USP5 promotes OS cell metastasis and progression by activating the Hh/Gli1 pathway.
  • USP5 stabilizes and deubiquitinates Gli1, mediating its oncogenic effects in OS.

Conclusions:

  • USP5 plays a critical role in osteosarcoma pathogenesis by activating the Hh/Gli1 signaling pathway.
  • USP5 is a potential diagnostic biomarker and therapeutic target for osteosarcoma.

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