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Classic SRY-box protein SOX7 functions as a tumor suppressor regulating WNT signaling and is methylated in renal cell

Lu Wang1, Yu Fan1, Lian Zhang1

  • 1Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|June 30, 2018
PubMed

Insights

SRY-related high mobility group box 7 (SOX7) acts as a tumor suppressor in renal cell carcinoma (RCC). It is frequently silenced by methylation, inhibiting RCC cell growth and WNT signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • SRY-related high mobility group box 7 (SOX7) is implicated in tumorigenesis but its role in renal cell carcinoma (RCC) is unclear.
  • SOX7 is a high mobility group protein known to be downregulated in various cancers.

Purpose of the Study:

  • To investigate the alterations and biological functions of SOX7 in the pathogenesis of renal cell carcinoma (RCC).
  • To determine the mechanism of SOX7 inactivation and its impact on RCC progression.

Main Methods:

  • Analysis of SOX7 expression in normal kidney tissues and RCC cell lines/tumors.
  • Investigation of promoter CpG methylation as a mechanism for SOX7 silencing.
  • Functional studies involving SOX7 restoration and knockdown in RCC cell lines.
  • Assessment of WNT signaling pathway activation and epithelial-mesenchymal transition (EMT) induction.

Main Results:

  • SOX7 is broadly expressed in normal tissues but frequently downregulated in RCC.
  • Promoter CpG methylation is identified as a key mechanism for SOX7 silencing in RCC, reversible by demethylation.
  • SOX7 methylation is prevalent in primary RCC tumors but rare in normal kidney tissues.
  • Restoring SOX7 inhibits RCC cell proliferation by inducing G0/G1 arrest.
  • SOX7 knockdown accelerates RCC cell proliferation.
  • SOX7 inactivation activates WNT signaling and promotes EMT.

Conclusions:

  • SOX7 functions as a tumor suppressor in renal cell carcinoma (RCC).
  • Frequent inactivation of SOX7 in RCC is mediated by promoter CpG methylation.
  • SOX7 regulates WNT signaling and epithelial-mesenchymal transition, impacting RCC pathogenesis.
Keywords:
CpG methylationSRY-related high mobility groupepithelial to mesenchymal transitionpromoterrenal cancer

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