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RBBP8/CtIP suppresses P21 expression by interacting with CtBP and BRCA1 in gastric cancer

Yang Yu1, Lei Chen1, Guiping Zhao1

  • 1Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, 100050, Beijing, China.

Oncogene
|October 23, 2019
PubMed

Insights

RB Binding Protein 8 (RBBP8) promotes gastric cancer cell growth by inhibiting P21 expression. RBBP8 facilitates cell cycle progression and recruits a complex that deacetylates the P21 promoter, suppressing its transcription.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • RB Binding Protein 8 (RBBP8) is implicated in DNA repair in cancers.
  • Its specific roles in gastric carcinogenesis remain unclear.

Purpose of the Study:

  • To investigate the function and mechanism of RBBP8 in gastric cancer.
  • To elucidate RBBP8's role in gastric carcinogenesis.

Main Methods:

  • Immunohistochemistry on gastric tissues.
  • Cell proliferation and colony formation assays.
  • Co-immunoprecipitation, immunofluorescence, HDAC activity assays, and Chromatin immunoprecipitation (ChIP).

Main Results:

  • RBBP8 expression is upregulated in gastric intraepithelial neoplasia and cancer.
  • RBBP8 knockdown inhibits proliferation by affecting G1/S transition and Cyclin D1/CDK4 levels.
  • RBBP8 interacts with BRCA1 and CtBP, enhancing BRCA1 nuclear localization.
  • RBBP8 suppresses P21 expression and transcription via CtBP-mediated histone deacetylation at the P21 promoter.

Conclusions:

  • RBBP8 promotes gastric cancer cell G1/S transition by inhibiting P21.
  • RBBP8 functions in chromatin modification by recruiting CtBP to deacetylate the P21 promoter, thus suppressing its transcription.

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