RAI14 Promotes Melanoma Progression by Regulating the FBXO32/c-MYC Pathway

Int J Mol Sci. 2022 Oct 10;23(19):12036. doi: 10.3390/ijms231912036.

Abstract

Melanoma originates from the malignant transformation of melanocytes. Compared with other skin cancers, melanoma has a higher fatality rate. The 5-year survival rate of patients with early-stage primary melanoma through surgical resection can reach more than 90%. However, the 5-year survival rate of patients with metastatic melanoma is only 25%. Therefore, accurate assessment of melanoma progression is critical. Previous studies have found that Retinoic Acid Induced 14(RAI14) is critical in tumorigenesis. However, the biological function of RAI14 for the development of melanoma is unclear. In this study, RAI14 is highly expressed in melanoma and correlated with prognosis. The expression of RAI14 can affect the proliferation, migration and invasion of melanoma cells. F-Box Protein 32(FBXO32) is an E3 ubiquitin ligase of c-MYC. We found that RAI14 affects the transcriptional expression of FBXO32 and regulates the stability of c-MYC. These results suggest that RAI14 play an important role in the growth of melanoma and is expected to be a therapeutic target for melanoma.

Keywords: RAI14; c-MYC; melanoma; proliferation; ubiquitination.

MeSH terms

  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic
  • Cytoskeletal Proteins* / metabolism
  • F-Box Proteins* / genetics
  • F-Box Proteins* / metabolism
  • Humans
  • Melanoma* / genetics
  • Melanoma* / pathology
  • Muscle Proteins / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Skin Neoplasms*
  • Transcription Factors* / metabolism
  • Tretinoin / metabolism
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Cytoskeletal Proteins
  • F-Box Proteins
  • MYC protein, human
  • Muscle Proteins
  • Proto-Oncogene Proteins c-myc
  • RAI14 protein, human
  • Transcription Factors
  • Tretinoin
  • FBXO32 protein, human
  • SKP Cullin F-Box Protein Ligases
  • Ubiquitin-Protein Ligases

Grants and funding

This research was supported by the Natural Science Foundation of Chongqing (cstc2022ycjh-bgzxm0145).