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Sox15 Methylation Inhibits Cell Proliferation Through Wnt Signaling in Hepatocellular Carcinoma

Bajin Wei1,2,3,4, Hao Chen5, Xiaobin Chen5

  • 1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Frontiers in Oncology
|April 8, 2022
PubMed

Insights

SRY-Box Transcription Factor 15 (Sox15) acts as a tumor suppressor in hepatocellular carcinoma (HCC). Reduced Sox15 expression and promoter methylation correlate with poor HCC prognosis, potentially via the Wnt pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • SRY-Box Transcription Factor 15 (Sox15) expression is reduced in various tumors due to DNA methylation, but its role in hepatocellular carcinoma (HCC) is unclear.
  • Understanding Sox15's function and regulation in HCC is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To investigate the clinical significance and molecular mechanisms of Sox15 in HCC.
  • To determine the correlation between Sox15 expression, promoter methylation, and HCC patient prognosis.

Main Methods:

  • Analysis of Sox15 expression and prognosis using GEPIA and OncoLnc databases.
  • Assessment of Sox15 promoter CpG-site methylation in relation to HCC prognosis.
  • In vitro studies involving ectopic Sox15 expression in HCC cell lines (LM3, HUH7, SK-hep-1).
  • In vivo xenograft tumor models in nude mice to evaluate Sox15's effect on tumorigenesis.
  • Investigation of Sox15's impact on the Wnt signaling pathway.

Main Results:

  • Sox15 expression is reduced in HCC and positively correlates with improved patient prognosis.
  • Hypermethylation of the Sox15 promoter CpG site is associated with a poorer HCC prognosis.
  • Ectopic Sox15 expression significantly inhibited HCC cell growth in vitro and suppressed tumor formation in vivo.
  • Sox15 was found to inactivate the Wnt signaling pathway in both in vitro and in vivo HCC models.

Conclusions:

  • Sox15 functions as a tumor suppressor in HCC by inactivating the Wnt pathway.
  • Both Sox15 expression levels and its promoter's CpG-site methylation are independent prognostic factors for HCC.
Keywords:
HCCSOX15Wnt signalingcell proliferationmethylation

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