Epigenetic silencing of KCTD8 promotes hepatocellular carcinoma growth by activating PI3K/AKT signaling

Epigenomics. 2024;16(13):929-944. doi: 10.1080/17501911.2024.2370590. Epub 2024 Jul 18.

Abstract

Aim: The aim of current study is to explore the epigenetic changes and function of KCTD8 in human hepatocellular carcinoma (HCC). Materials & methods: HCC cell lines and tissue samples were employed. Methylation specific PCR, flow cytometry, immunoprecipitation and xenograft mouse models were used.Results: KCTD8 was methylated in 44.83% (104/232) of HCC and its methylation may act as an independent poor prognostic marker. KCTD8 expression was regulated by DNA methylation. KCTD8 suppressed HCC cell growth both in vitro and in vivo via inhibiting PI3K/AKT pathway.Conclusion: Methylation of KCTD8 is an independent poor prognostic marker, and epigenetic silencing of KCTD8 increases the malignant tendency in HCC.

Keywords: DNA methylation; KCTD8; PI3K/AKT signaling pathway; hepatocellular carcinoma; tumor suppressor.

Plain language summary

[Box: see text].

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction*

Substances

  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • KCTD8 protein, human