TRIM14 regulates melanoma malignancy via PTEN/PI3K/AKT and STAT3 pathways

Aging (Albany NY). 2021 May 11;13(9):13225-13238. doi: 10.18632/aging.203003. Epub 2021 May 11.

Abstract

Melanoma is one of the most aggressive cancers with poor overall survival. To date, there are still few effective methods for the treatment of melanoma. TRIM14 was previously reported to be an important oncogene in many tumors. Nevertheless, the roles of TRIM14 in melanoma remain unknown. In this study, we found that TRIM14 was abnormally upregulated in melanoma cell lines. Knockdown of TRIM14 suppressed melanoma cell proliferation, migration, invasion, epithelial-mesenchymal transition, and melanin synthesis. Overexpression of TRIM14 had opposite effects on the cellular functions of melanoma cell lines. Further study revealed that TRIM14 knockdown increased PTEN protein levels, which in turn inactivated AKT and STAT3 pathways. Moreover, blocking AKT or STAT3 pathway with a specific inhibitor could partially reverse the promotion of melanoma malignancy mediated by TRIM14 overexpression. In addition, in vivo assay also supported the above findings. These results indicated that TRIM14 might be a promising target for melanoma treatment.

Keywords: AKT; STAT3; TRIM14; melanoma.

MeSH terms

  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma, Cutaneous Malignant
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Tripartite Motif Proteins / genetics
  • Tripartite Motif Proteins / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • TRIM14 protein, human
  • Tripartite Motif Proteins
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human