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      https://www.ias.ac.in/article/fulltext/jbsc/045/0002

    • Keywords

       

      Cancer; differentiation; dual-histone reader; ZMYND8

    • Abstract

       

      Accumulating evidences indicate the involvement of epigenetic deregulations in cancer. While some epigeneticregulators with aberrant functions in cancer are targeted for improving therapeutic outcome in patients,reinstating the functions of tumor-suppressor-like epigenetic regulators might further potentiate anti-cancertherapies. Epigenetic reader zinc-finger MYND-type-containing 8 (ZMYND8) has been found to be endowedwith multiple anti-cancer functions like inhibition of tumor cell migration and proliferation. Here, we reportanother novel tumor suppressor role of ZMYND8 as an inducer of differentiation in breast cancer cells, byupregulating differentiation genes. Interestingly, we also demonstrated that ZMYND8 mediates all its antitumorroles through a common dual-histone mark binding to H4K16Ac and H3K36Me2. We validated thesefindings by both biochemical and biophysical analyses. Furthermore, we also confirmed the differentiationinducingpotential of ZMYND8 in vivo, using 4T1 murine breast cancer model in Balb/c mice. Differentiationtherapy holds great promise in cancer therapy, since it is non-toxic and makes the cancer cells therapysensitive.In this scenario, we propose epigenetic reader ZMYND8 as a potential therapeutic candidate fordifferentiation therapy in breast cancer.

    • Author Affiliations

       

      SHRAVANTI MUKHERJEE1 SABYASACHI SEN1 SANTANU ADHIKARY1 2 AMRITA SENGUPTA1 PRATITI MANDAL3 DIPAK DASGUPTA1 PARTHA CHAKRABARTI3 SIDDHARTHA ROY2 CHANDRIMA DAS1 4

      1. Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata 700 064, India
      2. Structural Biology & Bioinformatics Division, CSIR–Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700 032, India
      3. Cell Biology and Physiology Division, CSIR–Indian Institute of Chemical Biology, Kolkata 700 032, India
      4. Homi Bhaba National Institute, Mumbai, India
    • Dates

       
  • Journal of Biosciences | News

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