The Histone H3K27me3 Demethylases KDM6A/B Resist Anoikis and Transcriptionally Regulate Stemness-Related Genes

• DOI: 10.3389/fcell.2022.780176
• Publication Date: 2022-02-02T05:24:02Z
• Authors: Mohammed Razeeth ...; Mazin Zamzami; Hani Choudhry; Firoz Ahmed; Bushra Ateeq; Mohammad Imran Khan
• Keywords: Demethylase; Anoikis; Ectopic expression

Epithelial cancer cells that lose attachment from the extracellular matrix (ECM) to seed in a distant organ often undergo anoikis's specialized form of apoptosis. Recently, KDM3A (H3K9 demethylase) has been identified as critical effector anoikis cells. However, whether other histone demethylases are involved promoting or resisting remains elusive. We screened major and found both H3K27 demethylases, namely, KDM6A/B were highly expressed during ECM detachment. Inhibition activity by using specific inhibitor results reduced sphere formation capacity increased Knockout KDM6B leads loss stem cell properties solitary Furthermore, we maintains stemness transcriptionally regulating expression genes SOX2, SOX9, CD44 detached occupies promoter region SOX2 regulate their epigenetically. also noticed an occupancy HIF1α KDM6B, suggesting its regulatory role maintaining hypoxia This observation was further strengthened significant positive association various types. Overall, our reveal novel transcriptional program regulates resistance against stemness-like properties.