A5052583294- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Cardiac Ischemia and Reperfusion
- Air Quality and Health Impacts
- Adipose Tissue and Metabolism
- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
- Viral-associated cancers and disorders
- Peroxisome Proliferator-Activated Receptors
- Cancer, Lipids, and Metabolism
- Cancer Research and Treatments
- Mesenchymal stem cell research
- Birth, Development, and Health
- Histone Deacetylase Inhibitors Research
- Traditional Chinese Medicine Analysis
- Autophagy in Disease and Therapy
- Cancer-related gene regulation
- Mechanisms of cancer metastasis
Johns Hopkins University
2020-2025
Johns Hopkins Medicine
2020-2025
Dalian Medical University
2013-2024
Sun Yat-sen University
2015-2024
Sun Yat-sen University Cancer Center
2024
National Sun Yat-sen University
2024
Zhejiang Chinese Medical University
2024
Shantou University
2024
Shantou University Medical College
2024
China International Science and Technology Cooperation
2024
Abstract Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) enriched in breast cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH + subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability tumor growth. Conversely, high levels enhance BCSC properties are correlated with poor overall...
Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cells (BCSCs) express high levels of H19, and ectopic overexpression significantly promotes cell clonogenicity, migration mammosphere-forming ability. Conversely, silencing represses these BCSC properties. In concordance, knockdown markedly inhibits tumor growth suppresses tumorigenesis...
Aberrant RNA splicing produces alternative isoforms of genes to facilitate tumor progression, yet how this process is regulated by oncogenic signal remains largely unknown. Here, we unveil that non-canonical activation nuclear AURKA promotes an suppressor RBM4 directed m6A reader YTHDC1 in lung cancer. Nuclear translocation a prerequisite for aberrant splicing, specifically triggering from the full isoform (RBM4-FL) short (RBM4-S) kinase-independent manner. RBM4-S functions as promoter...
Polymorphism drives survival under stress and provides adaptability. Genetic polymorphism of ribosomal RNA (rRNA) genes derives from internal repeat variation this multicopy gene, interindividual variation. A considerable amount rRNA sequence heterogeneity has been proposed but challenging to estimate given the scarcity accurate reference sequences. We identified four rDNA copies on chromosome 21 (GRCh38) with 99% similarity recently introduced KY962518.1. customized a GATK bioinformatics...
Application of differentiation therapy targeting cellular plasticity for the treatment solid malignancies has been lagging. Nasopharyngeal carcinoma (NPC) is a distinctive cancer with poor and high prevalence Epstein-Barr virus (EBV) infection. Here, we show that expression EBV latent protein LMP1 induces dedifferentiated stem-like status through transcriptional inhibition CEBPA. Mechanistically, upregulates STAT5A recruits HDAC1/2 to CEBPA locus reduce its histone acetylation. HDAC restored...
Introduction: Preeclampsia (PE) is a gestational hypertensive disease with unclear pathogenesis. This study aimed to identify the genes that play an important role in determining pathogenesis of PE using bioinformatics analysis and fundamental researches. Materials methods: Datasets from Gene Expression Omnibus (GEO) database were used screen for differentially expressed (DEGs). The NCBI, SangerBox, other databases analyze functions DEGs. Targetscan7, miRWalk, ENCORI, DIANA TOOLS, CircBank...
Glucocorticoid (GC) resistance remains a major obstacle to successful treatment of lymphoid malignancies. Till now, the precise mechanism GC unclear. In present study, dexamethasone (Dex) inhibited cell proliferation, arrested cycle in G0/G1-phase, and induced apoptosis Dex-sensitive acute lymphoblastic leukemia cells. However, Dex failed cause death Dex-resistant malignant Intriguingly, we found that autophagy was by resistant cells, as indicated autophagosomes formation, LC3-I LC3-II...
Cancer stem cells (CSCs) are considered to be responsible for tumor relapse and metastasis, which serve as a potential therapeutic target cancer. Aspirin has been shown reduce cancer risk mortality, particularly in colorectal However, the CSCs-suppressing effect of aspirin its relevant mechanisms remain unclear.CCK8 assay was employed detect cell viability. Sphere formation assay, colony ALDH1 were performed identify effects on CSC properties. Western blotting expression stemness factors....
Abstract Fine particulate matter (PM 2.5 ) is suggested to pose a severe risk the kidneys by inducing functional degradation and chronic kidney diseases (CKD). This study aims explore nephrotoxicity of PM exposure underlying mechanism. Herein, based on UK Biobank, it found that per interquartile range (IQR) increase in associated with 6% (95% CI: 1%–11%), 7% 3%–11%), 9% 4%–13%), 11% 9%–13%), 10% 8%–12%) nephritis, hydronephrosis, stone, acute renal failure, CKD, respectively. In experimental...
Abstract Increased ribosome biogenesis supports the need for high translation capacity and is a hallmark of cancer. Targeting this process presents promising strategy cancer therapy. We have developed first-in-class inhibitors RNA polymerase I (Pol I) transcription that block first rate-limiting step biogenesis, rRNA synthesis. find Pol inhibition by BMH-21 leads to significant decrease in active ribosomes. found broad, but heterogenous efficacy 18 cell lineages. To identify genes drive...
Background/Aims: Due to the lack of specific markers, isolation pure mesenchymal stem cells (MSCs) from murine bone marrow remains an unsolved problem. The present study explored whether neural ganglioside GD2 could serve as a single surface marker uniquely distinguish MSCs (mBM-MSCs) other elements. Methods: Immunocytochemistry and flow cytometry, in combination with quantitative RT-PCR, were used identify expression on culture-expanded mBM-MSCs. GD2+ GD2- fractions mBM-MSCs cultures sorted...
Abstract Tumor local invasion is the first step of metastasis cascade which remains key obstacle for cancer therapy. Collective cell migration plays a critical role in tumor invading into surrounding tissues. In vitro assays fail to assess collective real time manner. Herein we aim develop three-dimensional (3D) microfluidic model determine dynamic process. this model, breast cells induced by concentration gradient fetal bovine serum. We find that adopt movement rather than random manner...
RNA Polymerase I (Pol I) synthesizes rRNA, which is the first and rate-limiting step in ribosome biogenesis. Factors governing stability of polymerase complex are not known. Previous studies characterizing Pol inhibitor BMH-21 revealed a transcriptional stress-dependent pathway for degradation largest subunit I, RPA194. To identify E3 ligase(s) involved, we conducted cell-based RNAi screen ubiquitin genes. We establish Skp–Cullin–F-box protein F-box FBXL14 as an ligase show that binds to...
RNA Polymerase I (Pol I) has recently been recognized as a cancer therapeutic target. The activity of this enzyme is essential for ribosome biogenesis and universally activated in cancers. enzymatic multi-subunit complex resides its catalytic core composed RPA194, RPA135, RPA12, subunit with functions cleavage, transcription initiation elongation. Here we explore whether RPA12 influences the regulation RPA194 human cells. We use specific small-molecule Pol inhibitor BMH-21 that inhibits...
Objective: The long-noncoding RNAs (lncRNAs) have been identified as key players in diverse cellular processes non-small cell lung cancer (NSCLC). However, the understanding of biological functions and detailed mechanisms lncRNAs is still limited. Herein, lncRNA susceptibility candidate 9 (CASC9) on NSCLC progression investigated. Materials Methods: Expressions CASC9, HuR division cycle 6 (CDC6) tissues were detected with quantitative real-time polymerase chain reaction (qRT-PCR). counting...
Abstract Ribosome biosynthesis is a cancer vulnerability executed by targeting RNA polymerase I (Pol I) transcription. We developed advanced, specific Pol inhibitors to identify drivers of this sensitivity. By integrating multi-omics features and drug sensitivity data from large cell panel, we discovered that RPL22 frameshift mutation conferred inhibitor in microsatellite instable cancers. Mechanistically, directly interacts with 28S rRNA mRNA splice junctions, functioning as splicing...
Breast cancer stem cells are responsible for initiation, progression, and drug resistance. However, effective targeting strategies against the cell subpopulation still limited. Here, we unveil two splice variants of very-low-density lipoprotein receptor, VLDLR-I -II, which highly expressed in breast cells. In cells, VLDLR silencing suppresses sphere formation abilities vitro tumor growth vivo. We find that knockdown induces transition from self-renewal to quiescence. Surprisingly,...
Abstract The goal of this study was to identify cancer types with synthetic vulnerability RNA polymerase I (Pol I) inhibitors and resolve mechanistic underpinnings vulnerability. Specific selective Pol inhibitors, pioneered by our group, block the transcription rRNA, which is rate-limiting step in ribosome biogenesis protein synthesis. We conducted unbiased large-scale cell line screens performed correlative analyses using DepMap Achilles databases features that sensitize cells these...
Tellurium is a rare element, and ammonium trichloro (dioxoethylene-o,o') tellurate (AS101) the most bioactive molecule among several synthetic tellurium compounds. AS101 was found to be immunomodulatory can modulate types of cytokines. However, effect on tumor metastasis remains unclear. Heparanase, an endo-glucuronidase, cleaves heparin sulfate side chains proteoglycans cell surface, further leading degradation extracellular matrix. Heparanase also releases angiogenic factors in matrix,...
Airborne fine particulate matter (PM