MECOM and the PRDM gene family in uterine endometrial cancer: bioinformatics and experimental insights into pathogenesis and therapeutic potentials

Mol Med. 2024 Oct 28;30(1):190. doi: 10.1186/s10020-024-00946-0.

Abstract

To elucidate the expression profiles, methylation states, and clinicopathological significance of the PRDM gene family, focusing on the MECOM gene's role in uterine endometrial cancer (UCEC) and its molecular interactions with the TGF-beta signaling pathway. Our methodology combined detailed bioinformatics analyses using UALCAN and GEPIA with in vitro assessments in HEC-1-A cells. Techniques included CRISPR-Cas9 for gene editing and various cellular assays (CCK-8, flow cytometry, Transwell) to evaluate the effects of MECOM on cell proliferation, migration, and apoptosis, alongside Western blot analysis for protein regulation in the TGF-beta pathway. MECOM was upregulated in UCEC tissues, influencing tumor cell behavior significantly. Knockout studies demonstrated reduced proliferation and migration and increased apoptosis, while overexpression showed reverse effects. Mechanistically, MECOM modulated critical proteins within the TGF-beta pathway, impacting cell cycle dynamics and apoptotic processes. The PRDM gene family, particularly MECOM, plays a crucial role in the pathogenesis and progression of UCEC, suggesting its utility as a target for novel therapeutic interventions. Our findings offer valuable insights for future research and potential clinical application in managing uterine endometrial cancer.

Keywords: Expression patterns; MECOM; Methylation status; PRDM gene family; TGF-beta signaling pathway; Uterine endometrial cancer.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation*
  • Computational Biology* / methods
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / metabolism
  • Endometrial Neoplasms* / pathology
  • Endometrial Neoplasms* / therapy
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Multigene Family
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Transforming Growth Factor beta
  • Transcription Factors