TRIM47 promotes ovarian cancer cell proliferation, migration, and invasion by activating STAT3 signaling

Clinics (Sao Paulo). 2022 Oct 23:77:100122. doi: 10.1016/j.clinsp.2022.100122. eCollection 2022.

Abstract

Objectives: Tripartite Motif 47 (TRIM47) protein plays a prominent role in many cancers. This study aimed to investigate the biological roles of TRIM47 in ovarian cancer.

Methods: TRIM47 was knocked down and overexpressed in ovarian cancer cell lines SKOV3 and OVCAR3, and the effects on proliferation, clone formation, apoptosis, invasion, and growth of xenograft tumors in nude mice were determined. The expression levels of the selected candidates were tested by western blotting and quantitative real-time PCR.

Results: TRIM47 knockdown suppressed proliferation and encourages apoptosis of ovarian cancer cells. Similarly, TRIM47 knockdown suppressed ovarian cancer cell invasion, migration, and epithelial-mesenchymal transition. Ovarian cancer cell xenograft assays demonstrated that TRIM47 knockdown significantly inhibited tumor growth. Mechanistically, TRIM47 knockdown suppressed STAT3 phosphorylation and the expression of several downstream genes, including MCL-1, MMP2, and c-MYC. Silencing of STAT3 partially prevented TRIM47-induced tumor cell proliferation and invasion.

Conclusion: The present study's findings demonstrate that by activating STAT3 signaling, TRIM47 functions as an oncogene in ovarian cancer. TRIM47, therefore, appears to be a potential target for ovarian cancer prevention and/or therapy.

Keywords: Metastasis; Ovarian cancer; Proliferation; STAT3; TRIM47.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Ovarian Epithelial / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / pharmacology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness / genetics
  • Neoplasm Proteins / genetics
  • Nuclear Proteins / genetics
  • Ovarian Neoplasms* / genetics
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • STAT3 Transcription Factor / pharmacology

Substances

  • TRIM47 protein, human
  • Carrier Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • STAT3 protein, human
  • STAT3 Transcription Factor