A5102019452- Renal cell carcinoma treatment
- Ferroptosis and cancer prognosis
- Renal and related cancers
- Ovarian cancer diagnosis and treatment
- RNA modifications and cancer
- Organ Transplantation Techniques and Outcomes
- Liver Disease Diagnosis and Treatment
- Nanoplatforms for cancer theranostics
- Liver Disease and Transplantation
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Renal Transplantation Outcomes and Treatments
- Circular RNAs in diseases
- Advancements in Transdermal Drug Delivery
- Advanced biosensing and bioanalysis techniques
- Esophageal Cancer Research and Treatment
- Gastrointestinal disorders and treatments
- RNA Interference and Gene Delivery
- Gastrointestinal Tumor Research and Treatment
- Cancer-related molecular mechanisms research
- Cancer Genomics and Diagnostics
- Sphingolipid Metabolism and Signaling
- Metastasis and carcinoma case studies
- Immune cells in cancer
- Nuclear Structure and Function
The First Affiliated Hospital, Sun Yat-sen University
2015-2025
Sun Yat-sen University
2015-2025
Zhongshan Hospital
2015-2025
Fudan University
2015-2025
Nanjing University of Aeronautics and Astronautics
2024
University of Science and Technology of China
2023-2024
Renji Hospital
2020-2022
Shanghai Jiao Tong University
2020-2022
Shanghai Institute of Hematology
2022
Abstract Spindle and kinetochore-related complex subunit 3 (SKA3) is a component of the spindle complexes essential for accurate timing late mitosis. However, relationship between SKA3 hepatocellular carcinoma (HCC) has not yet been fully elucidated. Gene expression omnibus (GEO) (GSE62232, GSE45436, GSE6764, GSE36376) The Cancer Atlas (TCGA) datasets were analyzed to identify differential genes. Cell proliferation ability was using Counting Kit-8 (CCK8) assay plate clone formation assay,...
Patients with advanced hepatocellular carcinoma (HCC) continue to have a dismal prognosis. Potential biomarkers determine prognosis and select targeted therapies are urgently needed for patients HCC. This study aimed elucidate the role of UCK2 in HCC tumor progression. We performed screen public databases identify functional genes associated tumorigenesis, progression, outcome. identified uridine-cytidine kinase 2 (UCK2) as gene interest further study. promoting aggressiveness was...
Fatty liver disease is one of the leading causes chronic damage in western countries. Approximately 25% adults United States have fatty livers absence excessive alcohol consumption, a condition termed nonalcoholic (NAFLD). Little known about prevalence and genetic background NAFLD or factors that determine its development. In this study, we used Gene-Cloud Biotechnology Information bioinformatics platform to carry out comprehensive analysis identifying differentially expressed genes (DEGs),...
The myeloid-derived suppressor cell (MDSC)-mediated immunosuppressive tumor microenvironment (TME), where hypoxia counts for much, has greatly compromised the outcome of cancer immunotherapy. Here, we demonstrated a strategy selectively clearing intratumoral MDSCs. Specifically, 2-[2-[2-chloro-3-[(1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene]-1-cyclohexen-1-yl]ethenyl]-3,3-dimethyl-1-propylindolium iodide (IR-780) and metformin (Met) were coloaded into mesoporous silica...
Background: Obg-like ATPase 1 (OLA1) has been found to have a dual role in cancers.However, the relationship between OLA1 and hepatocellular carcinoma (HCC) remains unclear.Results: High expression of HCC was detected public datasets clinical samples, correlated with poor prognosis.Downregulation significantly inhibited proliferation, migration, invasion tumorigenicity cells.Mechanistically, GSEA showed that might promote tumor progression by regulating cell cycle apoptosis.In addition,...
<div>Abstract<p>Fumarate hydratase (FH) deficiency causes hereditary leiomyomatosis and renal cell carcinoma (RCC). FH-deficient tumors lack effective therapeutic options. Here, we utilized an epigenetic-focused single-guide RNA library to elucidate potential drug targets in tumors. The screen identified chromodomain helicase DNA-binding protein 6 (CHD6) as essential regulator of the growth FH-mutated RCC. Mechanically, FH loss induced fumarate-mediated succinylation inactivation...
<p>Characteristics of patients whose tumors were used for PDOs or PDXs experiments, Related to Figure 4&7.</p>
<p>Supplementary Figure 2. FH deficiency accumulates CHD6 via inactivating Keap1, related to 2&3. A. WB and co-IP analysis indicating no interactions between VHL proteins in WCLs of ACHN cells. B. (left) RT-qPCR (right) indicated the protein or mRNA levels control VHL-depleted RCC C. Schematic illustration Keap1 deletion mutants. The binding capacity is with symbol. D. Western blots showing vitro ubiquitination assays conducted by incubating reconstituted Keap1–CUL3–RBX1 E3...
<p>Summary of the epigenetic regulators showing decreased sgRNA abundance in UOK-262 and ACHN cells, respectively.</p>
<p>Supplementary Figure 5. CHD6/SMARCA2/4-coordinated SEs-promoter looping boosts the transcription of NF-κB-related targets, related to 6. A. 3C assay indicated genes in WT, CHD6-KO Caki-2 cells with or without DMF stimulation. “Pro” means input-pro, while “3C” primers targeting enhancer region. B. ChIP-qPCR H3K27ac markers promoters enhancers CCL2, ICAM1, BCL3 gene UOK-262 (n = 5). C. Immunoblotting analysis p65 immunoprecipitates CHD6 depletion. D. SMARCA2/4 SEs 5) restoration. E....
<p>Identification of super-enhancer-associated genes in DMF-treated ACHN cells, related to Figure 6.</p>
<p>Oligonucleotides, related to Methods.</p>
<p>Supplementary Figure 1. Library and cells used for in vivo epigenetic CRISPR screen, related to A. Schematic diagram of FH mutations distributions the indicated protein domains. B. Intracellular fumarate levels were measured a panel RCC cell lines. C. Lorenz curve showing distribution sgRNAs epigenetic-focused library. D. Workflow generation UOK- or ACHN-clones without Cas9 evaluating guides that persist upon tumour formation from initiating (TICs), with further screens. E. Western...
<p>Supplementary Figure 4. CHD6 activates NF-κB signaling to potentiate FH-deficient RCC malignancy, related 5. A. Volcano plot showing differentially expressed genes in UOK-262 cells upon knockdown. B. Unsupervised cluster analysis of control and knockdown cells. C. ATAC-seq signals the profiles OCRs across indicated peaks UOK262 with versus without D. Heatmap exhibiting significance transcription factor motifs enriched accessible loci derived from CHD6-KD motif is dominantly...
<p>Supplementary Figure 6. In vitro and in vivo assessment of AU-15330 efficacy against FH-deficient RCC multiple preclinical models, related to 7. A. Dose-response curves IC50 FH-intact or cells treated with AU-15330. B. UOK-262 AU-15330, AU-15139, AU-16235. C-D. Mouse weight changes measurements (C) (n = 5) complete blood counts (D) performed on vehicle control mice as Fig. 7A. E. Representative HE graphs showing the morphology critical organs an increased amount F. FH-mutated...
<p>Supplementary Figure 3. CHD6 is essential for FH-deficient RCC cells, related to 4. A-B. MTT analysis of FH-WT PRCC (A) or canonical ccRCC (B) cells with without CHD6-KD. C. Competition-based assay measure the effect CHD4 shRNA on growth UOK-262 (n = 3 per time point). CHD4-KD were identified by coexpression green fluorescent protein (GFP) (LMN vector). The percentage GFP+ was thus tracked over 12 days and normalized GFP day 2. D. Quantified BIL signals orthotopic (FH-intact Caki-2)...
<p>Supplementary Figure 1. Library and cells used for in vivo epigenetic CRISPR screen, related to A. Schematic diagram of FH mutations distributions the indicated protein domains. B. Intracellular fumarate levels were measured a panel RCC cell lines. C. Lorenz curve showing distribution sgRNAs epigenetic-focused library. D. Workflow generation UOK- or ACHN-clones without Cas9 evaluating guides that persist upon tumour formation from initiating (TICs), with further screens. E. Western...
<p>Supplementary Figure 4. CHD6 activates NF-κB signaling to potentiate FH-deficient RCC malignancy, related 5. A. Volcano plot showing differentially expressed genes in UOK-262 cells upon knockdown. B. Unsupervised cluster analysis of control and knockdown cells. C. ATAC-seq signals the profiles OCRs across indicated peaks UOK262 with versus without D. Heatmap exhibiting significance transcription factor motifs enriched accessible loci derived from CHD6-KD motif is dominantly...
<p>Supplementary Figure 6. In vitro and in vivo assessment of AU-15330 efficacy against FH-deficient RCC multiple preclinical models, related to 7. A. Dose-response curves IC50 FH-intact or cells treated with AU-15330. B. UOK-262 AU-15330, AU-15139, AU-16235. C-D. Mouse weight changes measurements (C) (n = 5) complete blood counts (D) performed on vehicle control mice as Fig. 7A. E. Representative HE graphs showing the morphology critical organs an increased amount F. FH-mutated...
<p>Characteristics of patients whose tumors were used for PDOs or PDXs experiments, Related to Figure 4&7.</p>
<p>Supplementary Figure 5. CHD6/SMARCA2/4-coordinated SEs-promoter looping boosts the transcription of NF-κB-related targets, related to 6. A. 3C assay indicated genes in WT, CHD6-KO Caki-2 cells with or without DMF stimulation. “Pro” means input-pro, while “3C” primers targeting enhancer region. B. ChIP-qPCR H3K27ac markers promoters enhancers CCL2, ICAM1, BCL3 gene UOK-262 (n = 5). C. Immunoblotting analysis p65 immunoprecipitates CHD6 depletion. D. SMARCA2/4 SEs 5) restoration. E....
<p>Supplementary Figure 2. FH deficiency accumulates CHD6 via inactivating Keap1, related to 2&3. A. WB and co-IP analysis indicating no interactions between VHL proteins in WCLs of ACHN cells. B. (left) RT-qPCR (right) indicated the protein or mRNA levels control VHL-depleted RCC C. Schematic illustration Keap1 deletion mutants. The binding capacity is with symbol. D. Western blots showing vitro ubiquitination assays conducted by incubating reconstituted Keap1–CUL3–RBX1 E3...
<p>Identification of super-enhancer-associated genes in DMF-treated ACHN cells, related to Figure 6.</p>
<p>Summary of the epigenetic regulators showing decreased sgRNA abundance in UOK-262 and ACHN cells, respectively.</p>
<p>Supplementary Figure 3. CHD6 is essential for FH-deficient RCC cells, related to 4. A-B. MTT analysis of FH-WT PRCC (A) or canonical ccRCC (B) cells with without CHD6-KD. C. Competition-based assay measure the effect CHD4 shRNA on growth UOK-262 (n = 3 per time point). CHD4-KD were identified by coexpression green fluorescent protein (GFP) (LMN vector). The percentage GFP+ was thus tracked over 12 days and normalized GFP day 2. D. Quantified BIL signals orthotopic (FH-intact Caki-2)...