URG4 mediates cell proliferation and cell cycle in osteosarcoma via GSK3β/β-catenin/cyclin D1 signaling pathway

Yayun Liu1,2, Yizhe Xi1, Gang Chen2

  • 1Department of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China.

Abstract

Insights

Upregulated gene 4 (URG4) promotes osteosarcoma progression by enhancing cell cycle and proliferation via the GSK3β/β-catenin/cyclin D1 pathway, suggesting it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma is a common malignant bone tumor with poor prognosis.
  • Upregulated gene 4 (URG4) expression correlates with osteosarcoma recurrence, metastasis, and poor outcomes.
  • The precise role and mechanisms of URG4 in osteosarcoma remain unclear.

Purpose of the Study:

  • To investigate the expression patterns of URG4 in osteosarcoma.
  • To elucidate the functional role of URG4 in osteosarcoma progression.
  • To explore the underlying molecular mechanisms of URG4 action in osteosarcoma.

Main Methods:

  • Immunohistochemistry (IHC), PCR, and Western blotting (WB) to assess URG4 expression.
  • In vitro assays (wound healing, Transwell, CCK-8, colony formation) to evaluate URG4's effect on cell migration, invasion, and proliferation.
  • Flow cytometry for cell cycle analysis and xenograft models for in vivo validation.

Main Results:

  • URG4 is highly expressed in osteosarcoma tissues and cells, linked to advanced stage and metastasis.
  • Downregulation of URG4 using siRNA suppressed osteosarcoma cell proliferation and cell cycle progression.
  • URG4 promotes osteosarcoma cell proliferation and tumorigenesis in vitro and in vivo via the pGSK3β/β-catenin/cyclin D1 signaling pathway.

Conclusions:

  • High URG4 expression in osteosarcoma drives cell cycle progression through the GSK3β/β-catenin/cyclin D1 signaling pathway.
  • URG4 represents a potential novel biomarker and therapeutic target for osteosarcoma treatment.

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