keyword
https://read.qxmd.com/read/38476765/mir-200c-reprograms-fibroblasts-to-recapitulate-the-phenotype-of-cafs-in-breast-cancer-progression
#21
JOURNAL ARTICLE
Zhao Lin, Megan E Roche, Víctor Díaz-Barros, Marina Domingo-Vidal, Diana Whitaker-Menezes, Madalina Tuluc, Guldeep Uppal, Jaime Caro, Joseph M Curry, Ubaldo Martinez-Outschoorn
Mesenchymal-epithelial plasticity driving cancer progression in cancer-associated fibroblasts (CAFs) is undetermined. This work identifies a subgroup of CAFs in human breast cancer exhibiting mesenchymal-to-epithelial transition (MET) or epithelial-like profile with high miR-200c expression. MiR-200c overexpression in fibroblasts is sufficient to drive breast cancer aggressiveness. Oxidative stress in the tumor microenvironment induces miR-200c by DNA demethylation. Proteomics, RNA-seq and functional analyses reveal that miR-200c is a novel positive regulator of NFκB-HIF signaling via COMMD1 downregulation and stimulates pro-tumorigenic inflammation and glycolysis...
2024: Cell Stress
https://read.qxmd.com/read/38473745/impact-of-histone-lysine-methyltransferase-suv4-20h2-on-cancer-onset-and-progression-with-therapeutic-potential
#22
REVIEW
Stela Papadaki, Christina Piperi
Histone lysine methyltransferase SUV4-20H2, a member of the suppressor of variegation 4-20 homolog (SUV4-20) family, has a critical impact on the regulation of chromatin structure and gene expression. This methyltransferase establishes the trimethylation of histone H4 lysine 20 (H4K20me3), a repressive histone mark that affects several cellular processes. Deregulated SUV4-20H2 activity has been associated with altered chromatin dynamics, leading to the misregulation of key genes involved in cell cycle control, apoptosis and DNA repair...
February 21, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38466034/high-tpx2-expression-results-in-poor-prognosis-and-sp1-mediates-the-coupling-of-the-cx3cr1-cxcl10-chemokine-pathway-to-the-pi3k-akt-pathway-through-targeted-inhibition-of-tpx2-in-endometrial-cancer
#23
JOURNAL ARTICLE
Mei Yang, Xiaogang Mao, Lin Li, Jiang Yang, Hui Xing, Chunfan Jiang
INTRODUCTION: Approximately 30% of individuals with advanced EC have unsatisfactory prognosis. Evidence suggests that TPX2 is frequently upregulated in malignancies and related to cancer progression. Its role and pathological mechanism in EC need further research. METHODS: GSEA and TPX2 expression, GO, KEGG, and prognostic analyses were performed with TCGA data by bioinformatic approaches. Relationships between TPX2 expression and clinicopathological parameters were investigated immunohistochemically and statistically...
March 2024: Cancer Medicine
https://read.qxmd.com/read/38461549/inhibition-of-intracellular-atp-synthesis-impairs-the-recruitment-of-homologous-recombination-factors-after-ionizing-radiation
#24
JOURNAL ARTICLE
Ryota Hayashi, Hikaru Okumura, Mayu Isono, Motohiro Yamauchi, Daiki Unami, Rahmartani Tania Lusi, Masamichi Yamamoto, Yu Kato, Yuki Uchihara, Atsushi Shibata
Ionizing radiation (IR)-induced double-strand breaks (DSBs) are primarily repaired by non-homologous end joining or homologous recombination (HR) in human cells. DSB repair requires adenosine-5'-triphosphate (ATP) for protein kinase activities in the multiple steps of DSB repair, such as DNA ligation, chromatin remodeling, and DNA damage signaling via protein kinase and ATPase activities. To investigate whether low ATP culture conditions affect the recruitment of repair proteins at DSB sites, IR-induced foci were examined in the presence of ATP synthesis inhibitors...
March 8, 2024: Journal of Radiation Research
https://read.qxmd.com/read/38461240/fli1-induces-erythroleukemia-through-opposing-effects-on-ubash3a-and-ubash3b-expression
#25
JOURNAL ARTICLE
Jie Wang, Chunlin Wang, Anling Hu, Kunlin Yu, Yi Kuang, Babu Gajendran, Eldad Zacksenhaus, Klarke Michael Sample, Xiao Xiao, Wuling Liu, Yaacov Ben-David
BACKGROUND: FLI1 is an oncogenic transcription factor that promotes diverse malignancies through mechanisms that are not fully understood. Herein, FLI1 is shown to regulate the expression of Ubiquitin Associated and SH3 Domain Containing A/B (UBASH3A/B) genes. UBASH3B and UBASH3A are found to act as an oncogene and tumor suppressor, respectively, and their combined effect determines erythroleukemia progression downstream of FLI1. METHODS: Promoter analysis combined with luciferase assays and chromatin immunoprecipitation (ChIP) analysis were applied on the UBASH3A/B promoters...
March 9, 2024: BMC Cancer
https://read.qxmd.com/read/38460130/a-therapeutically-targetable-positive-feedback-loop-between-lnc-hlx-2-7-hlx-and-myc-that-promotes-group-3-medulloblastoma
#26
JOURNAL ARTICLE
Keisuke Katsushima, Kandarp Joshi, Menglang Yuan, Brigette Romero, Mona Batish, Stacie Stapleton, George Jallo, Elayaraja Kolanthai, Sudipta Seal, Olivier Saulnier, Michael D Taylor, Robert J Wechsler-Reya, Charles G Eberhart, Ranjan J Perera
Recent studies suggest that long non-coding RNAs (lncRNAs) contribute to medulloblastoma (MB) formation and progression. We have identified an lncRNA, lnc-HLX-2-7, as a potential therapeutic target in group 3 (G3) MBs. lnc-HLX-2-7 RNA specifically accumulates in the promoter region of HLX, a sense-overlapping gene of lnc-HLX-2-7, which activates HLX expression by recruiting multiple factors, including enhancer elements. RNA sequencing and chromatin immunoprecipitation reveal that HLX binds to and activates the promoters of several oncogenes, including TBX2, LIN9, HOXM1, and MYC...
March 8, 2024: Cell Reports
https://read.qxmd.com/read/38459564/cd146-cafs-promote-progression-of-endometrial-cancer-by-inducing-angiogenesis-and-vasculogenic-mimicry-via-il-10-jak1-stat3-pathway
#27
JOURNAL ARTICLE
Zhicheng Yu, Qian Zhang, Sitian Wei, Yang Zhang, Ting Zhou, Qi Zhang, Rui Shi, Dmitry Zinovkin, Zahidul Islam Pranjol, Jun Zhang, Hongbo Wang
Heterogeneous cancer-associated fibroblasts (CAFs) play important roles in cancer progression. However, the specific biological functions and regulatory mechanisms involved in endometrial cancer have yet to be elucidated. We aimed to explore the potential mechanisms of heterogeneous CAFs in promoting endometrial cancer progression. The presence of melanoma cell adhesion molecule (MCAM; CD146) positive CAFs was confirmed by tissue multi-immunofluorescence (mIF), and fluorescence activated cell sorting (FACS)...
March 8, 2024: Cell Communication and Signaling: CCS
https://read.qxmd.com/read/38458187/arid1a-orchestrates-swi-snf-mediated-sequential-binding-of-transcription-factors-with-arid1a-loss-driving-pre-memory-b-cell-fate-and-lymphomagenesis
#28
JOURNAL ARTICLE
Darko Barisic, Christopher R Chin, Cem Meydan, Matt Teater, Ioanna Tsialta, Coraline Mlynarczyk, Amy Chadburn, Xuehai Wang, Margot Sarkozy, Min Xia, Sandra E Carson, Santo Raggiri, Sonia Debek, Benedikt Pelzer, Ceyda Durmaz, Qing Deng, Priya Lakra, Martin Rivas, Christian Steidl, David W Scott, Andrew P Weng, Christopher E Mason, Michael R Green, Ari Melnick
ARID1A, a subunit of the canonical BAF nucleosome remodeling complex, is commonly mutated in lymphomas. We show that ARID1A orchestrates B cell fate during the germinal center (GC) response, facilitating cooperative and sequential binding of PU.1 and NF-kB at crucial genes for cytokine and CD40 signaling. The absence of ARID1A tilts GC cell fate toward immature IgM+ CD80- PD-L2- memory B cells, known for their potential to re-enter new GCs. When combined with BCL2 oncogene, ARID1A haploinsufficiency hastens the progression of aggressive follicular lymphomas (FLs) in mice...
March 7, 2024: Cancer Cell
https://read.qxmd.com/read/38456209/histone-lactylation-bridges-metabolic-reprogramming-and-epigenetic-rewiring-in-driving-carcinogenesis-oncometabolite-fuels-oncogenic-transcription
#29
REVIEW
Yu Zhang, Hang Song, Meili Li, Peirong Lu
Heightened lactate production in cancer cells has been linked to various cellular mechanisms such as angiogenesis, hypoxia, macrophage polarisation and T-cell dysfunction. The lactate-induced lactylation of histone lysine residues is noteworthy, as it functions as an epigenetic modification that directly augments gene transcription from chromatin. This epigenetic modification originating from lactate effectively fosters a reliance on transcription, thereby expediting tumour progression and development. Herein, this review explores the correlation between histone lactylation and cancer characteristics, revealing histone lactylation as an innovative epigenetic process that enhances the vulnerability of cells to malignancy...
March 2024: Clinical and Translational Medicine
https://read.qxmd.com/read/38455425/e74-like-ets-transcription-factor-1-promotes-the-progression-of-pancreatic-cancer-by-regulating-doublecortin-like-kinase-1-janus-kinase-signal-transducer-and-activator-of-transcription-pathway
#30
JOURNAL ARTICLE
Bin Yang, Fengxian Shen, Yi Zhu, Wenjie Lu, Haolei Cai
This study was targeted at investigating the biological functions of E74-like ETS transcription factor 1 (ELF1) in pancreatic cancer (PC) and its underlying mechanism. ELF1 expression in PC tissues was detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Cell counting kit-8 (CCK-8) method, EdU method and flow cytometry were used to detect the cell proliferation and apoptosis of PC cell lines after transfection. A subcutaneous tumorigenesis model was constructed to validate the oncogenic role of ELF1 in vivo ...
2024: American Journal of Cancer Research
https://read.qxmd.com/read/38455406/yy1-induced-lncrna00511-promotes-melanoma-progression-via-the-mir-150-5p-adam19-axis
#31
JOURNAL ARTICLE
Ya-Ni Chen, Xin-Rui Fu, Hua Guo, Xin-Yao Fu, Ke-Song Shi, Tian Gao, Hai-Quan Yu
Increasing evidence indicates that long noncoding RNAs (lncRNAs) are therapeutic targets and key regulators of tumors development and progression, including melanoma. Long intergenic non-protein-coding RNA 511 (LINC00511) has been demonstrated as an oncogenic molecule in breast, stomach, colorectal, and lung cancers. However, the precise role and functional mechanisms of LINC00511 in melanoma remain unknown. This study confirmed that LINC00511 was highly expressed in melanoma cells (A375 and SK-Mel-28 cells) and tissues, knockdown of LINC00511 could inhibit melanoma cell migration and invasion, as well as the growth of subcutaneous tumor xenografts in vivo...
2024: American Journal of Cancer Research
https://read.qxmd.com/read/38453052/ras-protein-activator-like-2-rasal2-initiates-peritubular-capillary-rarefaction-in-hypoxic-renal-interstitial-fibrosis
#32
JOURNAL ARTICLE
Yu Zhang, Yiqiong Yang, Xiuxiu Hu, Bizhen Wei, Qian Shen, Chuanbing Shi, Pingsheng Chen
The progression of chronic kidney disease (CKD) often involves renal interstitial fibrosis (RIF) and subsequent loss of peritubular capillaries (PTCs), which enhances disease severity. Despite advancements in our understanding of fibrosis, effective interventions for reversing capillary loss remain elusive. Notably, RIF exhibits reduced capillary density, whereas renal cell carcinoma (RCC) shows robust angiogenesis under hypoxic conditions. Using RNA sequencing and bioinformatics, we identified differentially expressed genes (DEGs) in hypoxic human renal tubular epithelial cells (HK-2) and renal cancer cells (786-0)...
March 5, 2024: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/38438735/combined-anti-pd-1-hdac-inhibitor-and-anti-vegf-for-mss-pmmr-colorectal-cancer-a-randomized-phase-2-trial
#33
JOURNAL ARTICLE
Feng Wang, Ying Jin, Min Wang, Hui-Yan Luo, Wei-Jia Fang, Ying-Nan Wang, Yan-Xing Chen, Run-Jie Huang, Wen-Long Guan, Ji-Bin Li, Yu-Hong Li, Feng-Hua Wang, Xiao-Hua Hu, Yan-Qiao Zhang, Miao-Zhen Qiu, Lu-Lu Liu, Zi-Xian Wang, Chao Ren, De-Shen Wang, Dong-Sheng Zhang, Zhi-Qiang Wang, Wen-Ting Liao, Lin Tian, Qi Zhao, Rui-Hua Xu
Epigenetic modifications of chromatin, including histone acetylation, and tumor angiogenesis play pivotal roles in creating an immunosuppressive tumor microenvironment. In the randomized phase 2 CAPability-01 trial, we investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer...
March 4, 2024: Nature Medicine
https://read.qxmd.com/read/38426634/analysis-of-single-nuclear-chromatin-accessibility-reveals-unique-myeloid-populations-in-human-pancreatic-ductal-adenocarcinoma
#34
JOURNAL ARTICLE
Hillary G Pratt, Li Ma, Sebastian A Dziadowicz, Sascha Ott, Thomas Whalley, Barbara Szomolay, Timothy D Eubank, Gangqing Hu, Brian A Boone
BACKGROUND: A better understanding of the pancreatic ductal adenocarcinoma (PDAC) immune microenvironment is critical to developing new treatments and improving outcomes. Myeloid cells are of particular importance for PDAC progression; however, the presence of heterogenous subsets with different ontogeny and impact, along with some fluidity between them, (infiltrating monocytes vs. tissue-resident macrophages; M1 vs. M2) makes characterisation of myeloid populations challenging. Recent advances in single cell sequencing technology provide tools for characterisation of immune cell infiltrates, and open chromatin provides source and function data for myeloid cells to assist in more comprehensive characterisation...
March 2024: Clinical and Translational Medicine
https://read.qxmd.com/read/38425399/early-results-of-the-integrative-epigenomic-transcriptomic-landscape-of-colorectal-adenoma-and-cancer
#35
JOURNAL ARTICLE
You-Wang Lu, Zhao-Li Ding, Rui Mao, Gui-Gang Zhao, Yu-Qi He, Xiao-Lu Li, Jiang Liu
BACKGROUND: Aberrant methylation is common during the initiation and progression of colorectal cancer (CRC), and detecting these changes that occur during early adenoma (ADE) formation and CRC progression has clinical value. AIM: To identify potential DNA methylation markers specific to ADE and CRC. METHODS: Here, we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape...
February 15, 2024: World Journal of Gastrointestinal Oncology
https://read.qxmd.com/read/38424632/ubiquitylation-of-runx3-by-rna-binding-ubiquitin-ligase-mex3c-promotes-tumorigenesis-in-lung-adenocarcinoma
#36
JOURNAL ARTICLE
Zelai He, Huijun Zhang, Haibo Xiao, Xiangyu Zhang, Hongbo Xu, Ruifen Sun, Siwen Li
Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, but the early diagnosis rate is low. The RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in several cancers but its mechanism of action in LUAD is unclear. In this study, the biological activity of MEX3C was assessed in LUAD. MEX3C and RUNX3 mRNA levels in the tissues of LUAD patients were determined using reverse transcription‑quantitative PCR. The involvement of MEX3C in the growth and metastasis of LUAD cells was measured by EdU assay, CCK-8, colony formation, Transwell assay, TUNEL, and flow cytometry...
February 29, 2024: Journal of Translational Medicine
https://read.qxmd.com/read/38423594/cul4a-ubiquitin-ligase-is-an-independent-predictor-of-overall-survival-in-pancreatic-adenocarcinoma
#37
JOURNAL ARTICLE
Panagiotis Tavlas, Sofia Nikou, Christina Geramoutsou, Pinelopi Bosgana, Spyridon Champeris Tsaniras, Maria Melachrinou, Ioannis Maroulis, Vasiliki Bravou
BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with dismal prognosis. Genomic instability due to defects in cell-cycle regulation/mitosis or deficient DNA-damage repair is a major driver of PDAC progression with clinical relevance. Deregulation of licensing of DNA replication leads to DNA damage and genomic instability, predisposing cells to malignant transformation. While overexpression of DNA replication-licensing factors has been reported in several human cancer types, their role in PDAC remains largely unknown...
2024: Cancer Genomics & Proteomics
https://read.qxmd.com/read/38418875/sox17-enables-immune-evasion-of-early-colorectal-adenomas-and-cancers
#38
JOURNAL ARTICLE
Norihiro Goto, Peter M K Westcott, Saori Goto, Shinya Imada, Martin S Taylor, George Eng, Jonathan Braverman, Vikram Deshpande, Tyler Jacks, Judith Agudo, Ömer H Yilmaz
A hallmark of cancer is the avoidance of immune destruction. This process has been primarily investigated in locally advanced or metastatic cancer1-3 ; however, much less is known about how pre-malignant or early invasive tumours evade immune detection. Here, to understand this process in early colorectal cancers (CRCs), we investigated how naive colon cancer organoids that were engineered in vitro to harbour Apc-null, KrasG12D and Trp53-null (AKP) mutations adapted to the in vivo native colonic environment...
February 28, 2024: Nature
https://read.qxmd.com/read/38416570/csb-and-smarcal1-compete-for-rpa32-at-stalled-forks-and-differentially-control-the-fate-of-stalled-forks-in-brca2-deficient-cells
#39
JOURNAL ARTICLE
Nicole L Batenburg, Dana J Sowa, John R Walker, Sara N Andres, Xu-Dong Zhu
CSB (Cockayne syndrome group B) and SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent, regulator of chromatin, subfamily A-like 1) are DNA translocases that belong to the SNF2 helicase family. They both are enriched at stalled replication forks. While SMARCAL1 is recruited by RPA32 to stalled forks, little is known about whether RPA32 also regulates CSB's association with stalled forks. Here, we report that CSB directly interacts with RPA, at least in part via a RPA32C-interacting motif within the N-terminal region of CSB...
February 28, 2024: Nucleic Acids Research
https://read.qxmd.com/read/38401773/chemical-inhibitors-targeting-histone-methylation-readers
#40
REVIEW
Xiaolei Huang, Yichang Chen, Qin Xiao, Xinci Shang, Yanli Liu
Histone methylation reader domains are protein modules that recognize specific histone methylation marks, such as methylated or unmethylated lysine or arginine residues on histones. These reader proteins play crucial roles in the epigenetic regulation of gene expression, chromatin structure, and DNA damage repair. Dysregulation of these proteins has been linked to various diseases, including cancer, neurodegenerative diseases, and developmental disorders. Therefore, targeting these proteins with chemical inhibitors has emerged as an attractive approach for therapeutic intervention, and significant progress has been made in this area...
February 22, 2024: Pharmacology & Therapeutics
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