A5077540484- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- RNA modifications and cancer
- Biosensors and Analytical Detection
- Synthesis and biological activity
- Advanced biosensing and bioanalysis techniques
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Advanced Biosensing Techniques and Applications
- Cancer-related molecular mechanisms research
- Cancer-related gene regulation
- Chronic Myeloid Leukemia Treatments
- Asymmetric Synthesis and Catalysis
- Signaling Pathways in Disease
- Cancer Mechanisms and Therapy
- Cancer Immunotherapy and Biomarkers
- IL-33, ST2, and ILC Pathways
Guangdong Pharmaceutical University
2022-2024
Guangdong University of Technology
2022-2024
University of Pennsylvania
2022-2024
Guangxi Medical University
2022-2024
Cancer Research Institute
2022-2024
California Institute for Regenerative Medicine
2023-2024
California Institute of Technology
2022-2023
California University of Pennsylvania
2023
South China University of Technology
2023
Wuhan University
2016-2022
Abstract Colorectal cancer is one of the most common cancers in world. Although genomic mutations and single nucleotide polymorphisms have been extensively studied, epigenomic status colorectal patient tissues remains elusive. Here, together with transcriptomic analysis, we use ChIP-Seq to profile active enhancers at genome wide level paired (tumor adjacent from same patients). In total, sequence 73 pairs generate 147 H3K27ac ChIP-Seq, 144 RNA-Seq, whole sequencing 86 H3K4me3 samples. Our...
The chromatin reader eleven-nineteen leukemia (ENL) has been identified as a critical dependency in acute myeloid (AML), but its therapeutic potential remains unclear. We describe potent and orally bioavailable small-molecule inhibitor of ENL, TDI-11055, which displaces ENL from by blocking YEATS domain interaction with acylated histones. Cell lines primary patient samples carrying MLL rearrangements or NPM1 mutations are responsive to TDI-11055. A CRISPR-Cas9-mediated mutagenesis screen...
Acquired resistance to immunotherapy remains a critical yet incompletely understood biological mechanism. Here, using mouse model of pancreatic ductal adenocarcinoma (PDAC) study tumor relapse following immunotherapy-induced responses, we find that is reproducibly associated with an epithelial-to-mesenchymal transition (EMT), EMT-transcription factors ZEB1 and SNAIL functioning as master genetic epigenetic regulators this effect. in not due immunosuppression the immune microenvironment,...
Tissue damage elicits cell fate switching through a process called metaplasia, but how the starting is silenced and new activated has not been investigated in animals. In culture, pioneer transcription factors mediate "reprogramming" by opening chromatin sites for expression that can attract from cell's enhancers. Here we report SOX4 sufficient to initiate hepatobiliary metaplasia adult mouse liver, closely mimicking initiated toxic liver. lineage-traced cells, assessed timing of...
Hippo pathway is involved in tumorigenesis, and its regulation cytosol has been extensively studied, but regulatory mechanisms the nuclear are not clear. In current study, using a FBS-inducing model following serum starvation, we identified KDM3A, demethylase of histone H3K9me1/2, as positive regulator for hippo target genes. KDM3A promotes gene expression through two mechanisms, one to upregulate YAP1 expression, other facilitate H3K27ac on enhancers upregulation more relevant with...
Activation of transcription enhancers, especially super-enhancers, is one the critical epigenetic features tumorigenesis. However, very few studies have systematically identified enhancers specific in cancer tissues. Here, we studied change histone modifications MMTV-PyVT breast model, combining mass spectrometry-based proteomics and ChIP-seq-based epigenomics approaches. Some proteomic results were confirmed with western blotting IHC staining. An inhibitor H3K27ac was applied to study its...
Background and Aims Trimethylation of Lys36 on histone 3 (H3K36me3) catalyzed by methyltransferase SET domain‐containing 2 (SETD2) is one the most conserved epigenetic marks from yeast to mammals. SETD2 frequently mutated in multiple cancers acts as a tumor suppressor. Approach Results Here, using liver‐specific Setd2 depletion model, we found that deficiency sufficient trigger spontaneous HCC. Meanwhile, significantly increased size diethylnitrosamine‐induced HCC model. The mechanistic...
SETD2 controls neocortical area patterning and social behaviors.
Gain-of-function mutations in the histone acetylation "reader" eleven-nineteen-leukemia (ENL), found acute myeloid leukemia (AML) and Wilms tumor, are known to drive condensate formation gene activation cellular systems. However, their role tumorigenesis remains unclear. Using a conditional knock-in mouse model, we show that mutant ENL perturbs normal hematopoiesis, induces aberrant expansion of progenitors, triggers rapid onset aggressive AML. Mutant alters developmental inflammatory...
Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Up to 40% patients with DLBCL display refractory disease or relapse after standard chemotherapy treatment (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]), leading significant morbidity mortality. The molecular mechanisms chemoresistance in remain incompletely understood. Using a cullin–really interesting new gene (RING) ligase-based CRISPR-Cas9 library, we...
Background: Esophageal squamous cell carcinoma (ESCC), one of the leading causes cancer mortality worldwide, is a heterogeneous with diverse clinical manifestations. However, little known about epigenetic heterogeneity and its relevance for this prevalent cancer. Methods: We generated 7.56 Tb single-base resolution whole-genome bisulfite sequencing data 84 ESCC paired paraneoplastic tissues. The analysis identified inter- intratumor DNA methylation (DNAm) heterogeneity, epigenome-wide DNAm...
How disruptions to normal cell differentiation link tumorigenesis remains incompletely understood. Wilms tumor, an embryonal tumor associated with disrupted organogenesis, often harbors mutations in epigenetic regulators, but their role kidney development unexplored. Here, we show at single-cell resolution that a tumor-associated mutation the histone acetylation reader ENL disrupts mice by rewiring gene regulatory landscape. Mutant promotes nephron progenitor commitment while restricting...
Cisplatin‐based chemotherapy is the most commonly used treatment regimen for lung cancer. Cancer stem cells (CSCs) are postulated to be important promoters of drug resistance. We previously found that miR‐5100 overexpressed in cancer, but it unknown whether and how regulates cisplatin Here, we demonstrated was significantly up‐regulated CD44 + CD133 cancer (LCSCs) compared with non‐CSCs. Additionally, over‐expression increased CSC properties, cell growth, tumor sphere formation line A549 or...
AIM: To investigate the role of microRNA-34a (miR-34a) in induction apoptosis human lens epithelial (HLE-B3) cells. METHODS: The HLE-B3 cells was detected by Annexin V-PE detection kit after treatment with 200 μmol/L H2O2 for 24h and lentiviral miR-34a vector transfection. expression quantified quantitative real time polymerase chain reaction (qRT-PCR) response to exposure effects overexpression on B-cell lymphoma-2 (Bcl-2) silent information regulator 1 (SIRT1) determined qRT-PCR Western...
Abstract Upon virus infection, host cells use retinoic-acid–inducible geneI I (RIG-I)–like receptors to recognize viral RNA and activate type IFN expression. To investigate the role of protein methylation in antiviral signaling pathway, we screened all SET domain–containing proteins identified TTLL12 as a negative regulator RIG-I signaling. contains TTL domains, which are predicted have lysine methyltransferase tubulin tyrosine ligase activities, respectively. Exogenous expression represses...
Abstract Inflammation is one of the critical risk factors for colorectal cancer (CRC). However, mechanisms transition from colitis to CRC remain elusive. Recently, epigenetic changes have emerged as important regulatory colitis‐associated cancer. Here, a systematic epigenomic study histone modifications performed, including H3K4me1, H3K4me3, H3K27ac, H3K27me3 and H3K9me3, in an AOM‐DSS‐induced mouse model. In combination with transcriptomic data, authors generate dataset 105 deep sequencing...
Abstract The p53 tumor suppressor regulates multiple context-dependent suppressive programs. Although is mutated in ~90% of small cell lung cancer (SCLC) tumors, how mediates suppression this context unknown. Here, using a mouse model SCLC which endogenous expression can be conditionally and temporally regulated, we show that tumors maintain requirement for inactivation. However, identify subtype heterogeneity between such reactivation induces senescence subset while others, necrosis. We...