Browsing by Author "Xie, Qiqi"

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    Multi-omics analysis identifies glioblastoma dependency on H3K9me3 methyltransferase activity
    (Springer Nature, 2025-03-20) Xie, Qiqi; Du, Yuanning; Ghosh, Sugata; Rajendran, Saranya; Cohen-Gadol, Aaron A.; Baizabal, José-Manuel; Nephew, Kenneth P.; Han, Leng; Shen, Jia; Neurological Surgery, School of Medicine
    Histone H3 lysine 9 dimethylation and trimethylation (H3K9me2/3) are prevalent in human genomes, especially in heterochromatin and specific euchromatic genes. Methylation of H3K9 is modulated by enzymes such as SUV39H1, SUV39H2, SETDB1, SETDB2, and EHMT1/2, which influence cancer progression. This study reveals differential expression of these six H3K9 methyltransferases in tumors, with SUV39H1, SUV39H2, and SETDB1 showing significant links to cancer phenotypes. We developed the “H3K9me3 MtSig” (H3K9me3 methyltransferases signature) based on these findings. H3K9me3 MtSig is unique to various tumors, with prognostic significance and associations with key signaling pathways, especially in glioblastoma (GBM). Elevated H3K9me3 MtSig was observed in GBM samples, correlating with the G2/M cell cycle and reduced immune responses. H3K9me3-mediated repetitive sequence silencing by H3K9me3 MtSig contributed to these phenotypes, and inhibiting H3K9me3 MtSig in patient-derived GBM cells suppressed proliferation and increased immune responses. H3K9me3 MtSig serves as an independent prognostic factor and potential therapeutic target.
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    SUV39H1 maintains cancer stem cell chromatin state and properties in glioblastoma
    (American Society for Clinical Investigation, 2025-03-10) Li, Chunying; Xie, Qiqi; Ghosh, Sugata; Cao, Bihui; Du, Yuanning; Vo, Giau V.; Huang, Timothy Y.; Spruck, Charles; Carpenter, Richard L.; Wang, Y. Alan; Lu, Q. Richard; Nephew, Kenneth P.; Shen, Jia; Biochemistry and Molecular Biology, School of Medicine
    Glioblastoma (GBM) is the most lethal brain cancer, with GBM stem cells (GSCs) driving therapeutic resistance and recurrence. Targeting GSCs offers a promising strategy for preventing tumor relapse and improving outcomes. We identify SUV39H1, a histone-3, lysine-9 methyltransferase, as critical for GSC maintenance and GBM progression. SUV39H1 is upregulated in GBM compared with normal brain tissues, with single-cell RNA-seq showing its expression predominantly in GSCs due to super-enhancer-mediated activation. Knockdown of SUV39H1 in GSCs impaired their proliferation and stemness. Whole-cell RNA-seq analysis revealed that SUV39H1 regulates G2/M cell cycle progression, stem cell maintenance, and cell death pathways in GSCs. By integrating the RNA-seq data with ATAC-seq data, we further demonstrated that knockdown of SUV39H1 altered chromatin accessibility in key genes associated with these pathways. Chaetocin, an SUV39H1 inhibitor, mimics the effects of SUV39H1 knockdown, reducing GSC stemness and sensitizing cells to temozolomide, a standard GBM chemotherapy. In a patient-derived xenograft model, targeting SUV39H1 inhibits GSC-driven tumor growth. Clinically, high SUV39H1 expression correlates with poor glioma prognosis, supporting its relevance as a therapeutic target. This study identifies SUV39H1 as a crucial regulator of GSC maintenance and a promising therapeutic target to improve GBM treatment and patient outcomes.