A5070226552- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Cytokine Signaling Pathways and Interactions
- Glioma Diagnosis and Treatment
- Genetic Syndromes and Imprinting
- Testicular diseases and treatments
- Ethics and Legal Issues in Pediatric Healthcare
- NF-κB Signaling Pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Neurodegenerative Diseases
- Muscle Physiology and Disorders
- Cervical Cancer and HPV Research
- RNA and protein synthesis mechanisms
- MicroRNA in disease regulation
- Mitochondrial Function and Pathology
- Genital Health and Disease
- ATP Synthase and ATPases Research
- Histone Deacetylase Inhibitors Research
- Software-Defined Networks and 5G
- Viral Infections and Immunology Research
- Pituitary Gland Disorders and Treatments
- Long-Term Effects of COVID-19
Chinese Academy of Medical Sciences & Peking Union Medical College
2016-2025
Peking Union Medical College Hospital
2021-2024
Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences
2018-2023
Beijing Institute of Genomics
2011-2013
Chinese Academy of Sciences
2011-2013
Institut thématique Génétique, génomique et bioinformatique
2013
Jingdong (China)
2012
Centre International de Recherche sur le Cancer
2005-2011
Shanghai East Hospital
2009
Nagasaki University
2003
The role of Fat Mass and Obesity-associated protein (FTO) its substrate N6-methyladenosine (m6A) in mRNA processing adipogenesis remains largely unknown. We show that FTO expression m6A levels are inversely correlated during adipogenesis. depletion blocks differentiation only catalytically active restores Transcriptome analyses combination with m6A-seq revealed gene splicing grouped genes regulated by FTO. M6A is enriched exonic regions flanking 5′- 3′-splice sites, spatially overlapping...
N6-methyladenosine (m6A) is an important epitranscriptomic mark with high abundance in the brain. Recently, it has been found to be involved regulation of memory formation and mammalian cortical neurogenesis. However, while now established that m6A methylation occurs a spatially restricted manner, its functions specific brain regions still await elucidation. We identify widespread dynamic RNA developing mouse cerebellum further uncover distinct features continuous temporal-specific across...
Host cell metabolism can be modulated by viral infection, affecting survival or clearance. Yet the cellular rewiring mediated N6-methyladenosine (m6A) modification in interactions between virus and host remains largely unknown. Here we report that response to cells impair enzymatic activity of RNA m6A demethylase ALKBH5. This behavior increases methylation on α-ketoglutarate dehydrogenase (OGDH) messenger (mRNA) reduce its mRNA stability protein expression. Reduced OGDH decreases production...
N 6 -methyladenosine (m A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite relatively high m A levels brain, its potential functions brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using mouse to depict region-specific profile. RNA cerebellum are generally higher than those cerebral cortex. Heterogeneity of exists across different regions types neural cells including mRNAs be...
Abstract Neutrophil migration into the site of infection is necessary for antibacterial innate defense, whereas impaired neutrophil may result in excessive inflammation and even sepsis. The directed by extracellular signals such as chemokines has been extensively studied, yet intrinsic mechanism determining ability to migrate needs further investigation. N 6 -methyladenosine (m A) RNA modification important immunity inflammation, our preliminary data indicate downregulation m A demethylase...
SHH subgroup medulloblastoma (SHH-MB) is one of the most common malignant pediatric tumors that arises in cerebellum. Previously, we showed RNA m6A methylation participates regulation cerebellar development. Here investigate whether dysregulated contributes to tumorigenesis SHH-MB. We show high expression methyltransferase METTL3 associates with worse survival patients A large number hypermethylated transcripts are identified SHH-MB tumor cells by m6A-seq. find promotes progression via...
Regulation of actomyosin dynamics by post-transcriptional modifications in cytoplasmic actin is still poorly understood. Here we demonstrate that dioxygenase ALKBH4-mediated demethylation a monomethylated site (K84me1) regulates actin–myosin interaction and actomyosin-dependent processes such as cytokinesis cell migration. ALKBH4-deficient cells display elevated K84me1 levels. Non-muscle myosin II only interacts with unmethylated its proper recruitment to depend on ALKBH4. ALKBH4...
As a deubiquitinating enzyme (DUB), the physiological substrates of ataxin-3 (ATX-3) remain elusive, which limits our understanding its normal cellular function and that pathogenic mechanism spinocerebellar ataxia type 3 (SCA3). Here, we identify p53 to be novel substrate ATX-3. ATX-3 binds native polyubiquitinated deubiquitinates stabilizes by repressing degradation through ubiquitin (Ub)-proteasome pathway. deletion destabilizes p53, resulting in deficiency activity functions, whereas...
Although RNA m 6 A regulators have been implicated in the tumorigenesis of several different types tumors, including pancreatic cancer, their clinical relevance and intrinsic regulatory mechanism remain elusive. This study analyzed eight (METTL3, METTL14, WTAP, FTO, ALKBH5, YTHDF1-3) ductal adenocarcinoma (PDAC) found that only demethylase ALKBH5 serves as an independent favorable prognostic marker for this tumor. To better understand molecular underlying protective effect conferred by...
The entity of DNA N6-methyladenine (6mA) in mammals remains elusive and subsequently its roles diseases are poorly understood. Here we exploited a bacterial contamination-free ultrasensitive UHPLC-MS/MS assay to reassess 6mA human glioblastomas unveiled that (~0.08 ppm) is extremely rare. By the use two independent heavy stable isotope-labeling strategies, further prove observed solely generated by polymerase-mediated misinocorporation. In vitro experiments point toward generation...
We previously reported that the oncoproteins E6 and E7 from cutaneous human papillomavirus type 38 (HPV38) can immortalize primary keratinocytes in vitro sensitize transgenic mice to develop skin cancer vivo. Immunofluorescence staining revealed immortalized by HPV38 display fewer actin stress fibers than do control keratinocyte cells, raising possibility of a role viral remodeling cytoskeleton. In this study, we show induces fiber disruption phenomenon correlates with its ability...
Background: Alzheimer’s disease (AD) is the most common neurodegenerative characterized by pathological accumulation of b-amyloid and neurofibrillary tangles. Despite substantial progress in both basic clinical research on AD, detailed mechanism AD pathogenesis still elusive. RNA N6-methyladenosine methylation (m6A) predominant post-transcriptional modification eukaryotic mRNA, prominently enriched mammalian brain. Notably, m6A-modified showed significant changes during development...
Abstract SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected were analyzed. Compared to normal controls, resulted dysregulation genes involving diverse functions various examined tissues/organs, drastic changes cerebral cortex and right ventricle....
Constitutive activation of NF-κB signaling is a key event in virus- and non-virus-induced carcinogenesis. We have previously reported that cutaneous human papillomavirus type 38 (HPV38) displays transforming properties vitro vivo experimental models. However, the involvement HPV38-induced cell growth transformation remains to be determined. In this study, we showed HPV38 E6 E7 activate inhibition pathway with IκBα superrepressor sensitizes HPV38E6E7-immortalized keratinocytes tumor necrosis...
Abstract Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epigenetic mark in cancer, its precise role lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with breast cancer. Accompanying high expression of TET1 and TET2 proteins, large numbers genes the metastasis-positive primary tumors exhibit higher levels than those metastasis-negative tumors. contrast, TET protein decrease significantly within metastatic lesions nodes...
Dok1 is believed to be a mainly cytoplasmic adaptor protein which down-regulates mitogen-activated kinase activation, inhibits cell proliferation and transformation, promotes spreading migration. Here we show that shuttles between the nucleus cytoplasm. Treatment of cells with leptomycin B (LMB), specific inhibitor nuclear export signal (NES)-dependent receptor CRM1, causes accumulation Dok1. We have identified functional NES (348LLKAKLTDPKED359) plays major role in localization Src-induced...
Abstract Mitochondrial encephalomyopathies (ME) are frequently associated with mutations of mitochondrial DNA, but the pathogenesis a subset ME (sME) remains elusive. Here we report that haploinsufficiency inner membrane protein, Mic60, causes progressive neurological abnormalities insulted structure and neuronal loss in mice. In addition, Mic60 reduces potential cellular ATP production, increases reactive oxygen species, alters oxidative phosphorylation complexes neurons an age‐dependent...
Abstract Background Skeletal muscle atrophy, particularly ageing‐related muscular atrophy such as sarcopenia, is a significant health concern. Despite its prevalence, the underlying mechanisms remain poorly understood, and specific approved medications are currently unavailable. Deleted in breast cancer 1 (DBC1) well‐known regulator of senescence, metabolism or apoptosis. Recent reports suggest that DBC1 may also potentially regulate function, mice lacking exhibit weakness limpness. However,...