TRIM59 promotes osteosarcoma progression via activation of STAT3

Hum Cell. 2022 Jan;35(1):250-259. doi: 10.1007/s13577-021-00615-y. Epub 2021 Oct 9.

Abstract

Osteosarcoma (OS) is a common, highly malignant bone tumor. Tripartite motif-containing protein 59 (TRIM59) has been identified as a potential oncogenic protein involved in the initiation and progression of various human carcinomas. Nonetheless, the possible roles and molecular mechanisms of action of TRIM59 in OS remain unclear. In this study, we found that TRIM59 expression levels were frequently upregulated in OS tissues and cell lines. TRIM59 knockdown significantly suppressed the proliferation, migration, and invasion of OS cells and promoted OS cell apoptosis, whereas TRIM59 overexpression had the opposite effects. In vivo experiments demonstrated that TRIM59 knockdown suppressed OS tumor growth and metastasis in vivo. Furthermore, we found that TRIM59 directly interacted with phospho-STAT3 in OS cells. The downregulation of STAT3 levels attenuated TRIM59-induced cell proliferation and invasion. Taken together, our results indicate that TRIM59 promoted OS progression via STAT3 activation. Therefore, our study may provide a novel therapeutic target for OS.

Keywords: Cell proliferation; Osteosarcoma; STAT3; TRIM59; Tumor invasion.

MeSH terms

  • Apoptosis / genetics
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology*
  • Bone Neoplasms / therapy
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Expression*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness / genetics
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology*
  • Osteosarcoma / therapy
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / metabolism*
  • Tripartite Motif Proteins / genetics
  • Tripartite Motif Proteins / metabolism
  • Tripartite Motif Proteins / physiology*

Substances

  • Intracellular Signaling Peptides and Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • TRIM59 protein, human
  • Tripartite Motif Proteins