TRIM58 Interacts with Pyruvate Kinase M2 to Inhibit Tumorigenicity in Human Osteosarcoma Cells

Peng Yuan1, Yiyi Zhou1, Rui Wang1

  • 1Department of Orthopaedics, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214000, China.

Abstract

Insights

Tripartite motif containing 58 (TRIM58) acts as a tumor suppressor in osteosarcoma (OS). TRIM58 inhibits OS cell growth and regulates energy metabolism by interacting with pyruvate kinase M2 (PKM2).

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tripartite motif containing 58 (TRIM58) functions as an E3 ubiquitin ligase and is recognized as a tumor suppressor gene in various human cancers.
  • The specific biological role of TRIM58 in osteosarcoma (OS) remains largely uncharacterized.

Purpose of the Study:

  • To elucidate the function of TRIM58 in osteosarcoma (OS).
  • To investigate the underlying molecular mechanisms and signaling pathways of TRIM58 in OS.

Main Methods:

  • TRIM58 expression was manipulated in OS cells using RNA interference (RNAi) for silencing and lentiviral vectors for overexpression.
  • Cell proliferation was assessed using the cell counting kit-8 (CCK-8) assay, and apoptosis was analyzed via flow cytometry.
  • Gene expression levels were quantified using qRT-PCR and Western blot, while protein interactions were examined using co-immunoprecipitation (Co-IP) assays.

Main Results:

  • TRIM58 was found to be downregulated in human OS tissues.
  • Overexpression of TRIM58 significantly inhibited OS cell proliferation, glucose uptake, and lactate production, indicating its role in regulating energy metabolism.
  • TRIM58 was observed to interact with pyruvate kinase M2 (PKM2) in OS cells, potentially inhibiting PKM2 activity through enhanced polyubiquitination.

Conclusions:

  • This study reveals the tumor-suppressive function of TRIM58 in osteosarcoma.
  • The findings highlight TRIM58's involvement in regulating energy metabolism and its interaction with PKM2, offering insights into its signaling pathway in OS.

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