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VprBP directs epigenetic gene silencing through histone H2A phosphorylation in colon cancer. | LitMetric

AI Article Synopsis

  • Histone modification, specifically involving VprBP, plays a crucial role in the dysregulation of gene transcription associated with colon cancer.
  • VprBP is found to be overexpressed in colon cancer, leading to the phosphorylation of histone H2A at T120, which silences growth regulatory genes and boosts cancer cell proliferation.
  • The use of the VprBP inhibitor B32B3 in preclinical models shows promise in reducing tumor growth by reversing the harmful effects of H2AT120 phosphorylation, highlighting VprBP as a potential target for new treatments.

Article Abstract

Histone modification is aberrantly regulated in cancer and generates an unbalanced state of gene transcription. VprBP, a recently identified kinase, phosphorylates histone H2A on threonine 120 (T120) and is involved in oncogenic transcriptional dysregulation; however, its specific role in colon cancer is undefined. Here, we show that VprBP is overexpressed in colon cancer and directly contributes to epigenetic gene silencing and cancer pathogenesis. Mechanistically, the observed function of VprBP is mediated through H2AT120 phosphorylation (H2AT120p)-driven transcriptional repression of growth regulatory genes, resulting in a significantly higher proliferative capacity of colon cancer cells. Our preclinical studies using organoid and xenograft models demonstrate that treatment with the VprBP inhibitor B32B3 impairs colonic tumor growth by blocking H2AT120p and reactivating a transcriptional program resembling that of normal cells. Collectively, our work describes VprBP as a master kinase contributing to the development and progression of colon cancer, making it a new molecular target for novel therapeutic strategies.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486565PMC
http://dx.doi.org/10.1002/1878-0261.13068DOI Listing

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