A5100783595- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Cancer-related molecular mechanisms research
- Endoplasmic Reticulum Stress and Disease
- Drug Transport and Resistance Mechanisms
- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Cancer therapeutics and mechanisms
- Cancer Cells and Metastasis
- Cell death mechanisms and regulation
- Peptidase Inhibition and Analysis
- PI3K/AKT/mTOR signaling in cancer
- MicroRNA in disease regulation
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Immune Cell Function and Interaction
- Cancer Mechanisms and Therapy
- Cancer Research and Treatments
- Cancer, Lipids, and Metabolism
- Circadian rhythm and melatonin
Genome Institute of Singapore
2016-2025
Agency for Science, Technology and Research
2016-2025
National University of Singapore
2014-2024
Duke-NUS Medical School
2010-2024
Sunshine Coast University Hospital
2024
University of the Sunshine Coast
2024
Nanjing Medical University
2012-2024
East China University of Science and Technology
2024
Fudan University
2023-2024
Zhongshan Hospital
2023-2024
Polycomb-repressive complex 2 (PRC2)-mediated histone methylation plays an important role in aberrant cancer gene silencing and is a potential target for therapy. Here we show that S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin A (DZNep) induces efficient apoptotic cell death cells but not normal cells. We found DZNep effectively depleted cellular levels of PRC2 components EZH2, SUZ12, EED inhibited associated H3 Lys 27 (but 9 methylation). By integrating RNA interference...
Relapse to anti-HER2 monoclonal antibody (mAb) therapies, such as trastuzumab in HER2+ breast cancer (BC), is associated with residual disease progression due resistance therapy. Here, we identify interferon-γ inducible protein 16 (IFI16)-dependent STING signaling a significant determinant of responses BC. We show that down-regulation immune-regulated genes (IRG) specifically poor survival HER2+, but not other BC subtypes. Among IRG, IFI16 identified direct target EZH2, the underexpression...
Significance Colorectal cancer patients often relapse due to resistance chemotherapy. The tumor microenvironment is known contribute aggressiveness and chemoresistance, but the underlying mechanisms remain elusive. In current study, we have shown that cancer-associated fibroblasts (CAFs) which are present in can greatly promote of colorectal cells low-oxygen condition (hypoxia), CAFs-secreted growth factor TGF-β2 induce strong expression GLI2 , a gene therapy. As such, therapeutic targeting...
Nutrients are absorbed solely by the intestinal villi. Aging of this organ causes malabsorption and associated illnesses, yet its aging mechanisms remain unclear. Here, we show that aging-caused villus structural functional decline is regulated mTORC1, a sensor nutrients growth factors, which highly activated in stem progenitor cells geriatric mice. These phenotypes recapitulated cell-specific Tsc1 knockout Mechanistically, mTORC1 activation increases protein synthesis MKK6 augments p38...
Abstract The hypoxic tumor microenvironment has been implicated in immune escape, but the underlying mechanism remains elusive. Using an vitro culture system modeling human T cell dysfunction and exhaustion triple-negative breast cancer (TNBC), we find that hypoxia suppresses effector gene expression, including NK cells, resulting resistance to immunotherapy. We demonstrate hypoxia-induced factor 1α (HIF1α) interaction with HDAC1 concurrent PRC2 dependency causes chromatin remolding...
Inhibitors of histone deacetylases (HDACIs) are a new generation anticancer agents that selectively kill tumor cells. However, the molecular basis for their selectivity is not well understood. We investigated effects HDACIs on oncogenic Rb-E2F1 pathway, which frequently deregulated in human cancers. Here, we report cancer cells with elevated E2F1 activity, caused either by enforced expression, or E1A oncogene highly susceptible to HDACI-induced cell death. This E2F1-mediated apoptosis...
The Rb–E2F pathway drives cell cycle progression and proliferation, the molecular strategies safeguarding its activity are not fully understood. Here we report that E2F1 directly transactivates miR-449a/b . targets inhibits oncogenic CDK6 CDC25A , resulting in pRb dephosphorylation arrest at G1 phase, revealing a negative feedback regulation of pRb–E2F1 pathway. Moreover, miR-449 a/b expression cancer cells is epigenetically repressed through histone H3 Lys27 trimethylation, epigenetic drug...
Diabetic retinopathy is a chronic low‐grade inflammatory disease; however, the mechanisms remain elusive. In present study, we demonstrated that endoplasmic reticulum (ER) stress was activated in retina animal models of diabetes and oxygen‐induced (OIR). Induction ER by tunicamycin resulted significantly increased expression molecules retina. Inhibition chemical chaperone 4‐phenyl butyric acid ameliorated inflammation cultured human retinal endothelial cells exposed to hypoxia, retinas...
Drosophila males modulate the interpulse intervals produced during their courtship songs. These song cycles, which are altered by mutations in clock gene period, exhibit a species-specific variation that facilitates mating. We have used chimeric period constructs from melanogaster and simulans germline transformation experiments to map genetic control of rhythm difference small segment amino acid encoding information within this gene.
Epithelial-mesenchymal transition (EMT) in cancer cells plays a pivotal role determining metastatic prowess, but knowledge of EMT regulation remains incomplete. In this study, we defined critical functional for the Forkhead transcription factor FOXQ1 regulating breast cells. expression was correlated with high-grade basal-like cancers and associated poor clinical outcomes. RNAi-mediated suppression highly invasive human reversed EMT, reduced ability, alleviated other aggressive phenotypes...
The pero1 and the pers mutations in Drosophila melanogaster, which seem to eliminate or speed up, respectively, clocks underlying biological rhythmicity, were mapped single nucleotides. Chimeric DNA fragments consisting of well-defined wild-type plus mutant subsegments constructed, introduced into flies by germ-line transformation, assayed for activity. These experiments localized both a 1.7-kilobase fragment that is mostly coding DNA. Sequencing this subsegment from each showed completely...
CDKN1C (encoding tumor suppressor p57(KIP2)) is a cyclin-dependent kinase (CDK) inhibitor whose family members are often transcriptionally downregulated in human cancer via promoter DNA methylation. In this study, we show that repressed breast cells mainly through histone modifications. particular, targeted by methyltransferase EZH2-mediated H3 lysine 27 trimethylation (H3K27me3), and can be strongly activated inhibition of EZH2 synergy with deacetylase inhibitor. Consistent the...
Metastatic tumour recurrence due to failed treatments remains a major challenge of breast cancer clinical management. Here we report that interleukin-1 receptor-associated kinase 1 (IRAK1) is overexpressed in subset cancers, particular triple-negative (TNBC), where it acts drive aggressive growth, metastasis and acquired resistance paclitaxel treatment. We show IRAK1 overexpression confers TNBC growth advantage through NF-κB-related cytokine secretion metastatic cells exhibit gain...
Although 3-phosphoinositide-dependent protein kinase-1 (PDK1) has been predominately linked to the phosphoinositide 3-kinase (PI3K)-AKT pathway, it may also evoke additional signaling outputs promote tumorigenesis. Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn MYC and accumulation. We show PDK1-PLK1-MYC is critical for cancer cell growth survival, small-molecule inhibition PDK1/PLK1 provides an effective approach therapeutic targeting...
Transcriptional reactivation of telomerase reverse transcriptase (TERT) reconstitutes activity in the majority human cancers. Here, we found that ectopic TERT expression increases cell proliferation, while acute reductions levels lead to a dramatic loss proliferation without any change telomere length, suggesting effects could be independent. We observed determines growth rate cancer cells by directly regulating global protein synthesis independently its catalytic activity. Genome-wide...