keyword
https://read.qxmd.com/read/37838026/hic1-interacts-with-foxp3-multi-protein-complex-novel-pleiotropic-mechanisms-to-regulate-human-regulatory-t-cell-differentiation-and-function
#21
JOURNAL ARTICLE
Syed Bilal Ahmad Andrabi, Kedar Batkulwar, Santosh D Bhosale, Robert Moulder, Meraj Hasan Khan, Tanja Buchacher, Mohd Moin Khan, Ilona Arnkil, Omid Rasool, Alexander Marson, Ubaid Ullah Kalim, Riitta Lahesmaa
Transcriptional repressor, hypermethylated in cancer 1 (HIC1) participates in a range of important biological processes, such as tumor repression, immune suppression, embryonic development and epigenetic gene regulation. Further to these, we previously demonstrated that HIC1 provides a significant contribution to the function and development of regulatory T (Treg) cells. However, the mechanism by which it regulates these processes was not apparent. To address this question, we used affinity-purification mass spectrometry to characterize the HIC1 interactome in human Treg cells...
October 12, 2023: Immunology Letters
https://read.qxmd.com/read/37785623/investigating-the-potential-role-of-ikzf3-in-hpv-associated-carcinogenesis
#22
JOURNAL ARTICLE
A Ishag-Osman, A Calderon-Zavala, M Grace, K Munger
PURPOSE/OBJECTIVE(S): HPVs cause approximately 5% of all human cancers. They encode two viral transforming proteins, E6 and E7, that are consistently expressed in these cancers. The HPV E6 and E7 proteins contribute to carcinogenesis by binding and functionally compromising multiple cellular regulatory proteins, most prominently the p53 and retinoblastoma (pRB) tumor suppressors, respectively. To discover additional cellular regulatory circuits that are dysregulated by E6 and E7 expression, we performed RNA sequencing analyses of HPV16 E6 and E7 expressing primary human genital epithelial cells...
October 1, 2023: International Journal of Radiation Oncology, Biology, Physics
https://read.qxmd.com/read/37767768/transcriptional-heterogeneity-overcomes-super-enhancer-disrupting-drug-combinations-in-multiple-myeloma
#23
JOURNAL ARTICLE
Seth J Welsh, Benjamin G Barwick, Erin W Meermeier, Daniel L Riggs, Chang-Xin Shi, Yuan Xiao Zhu, Meaghen E Sharik, Megan T Du, Leslie D Abrego Rocha, Victoria M Garbitt, Caleb K Stein, Joachim L Petit, Nathalie Meurice, Yuliza Tafoya Alvarado, Rodrigo Fonseca, Kennedi T Todd, Sochilt Brown, Zachary J Hammond, Nicklus H Cuc, Courtney Wittenberg, Camille Herzog, Anna V Roschke, Yulia N Demchenko, Wei-Dong D Chen, Peng Li, Wei Liao, Warren J Leonard, Sagar Lonial, Nizar J Bahlis, Paola Neri, Lawrence H Boise, Marta Chesi, P Leif Bergsagel
Multiple myeloma (MM) is a malignancy that is often driven by MYC and that is sustained by IRF4, which are upregulated by super-enhancers. IKZF1 and IKZF3 bind to super-enhancers and can be degraded using immunomodulatory imide drugs (IMiDs). Successful IMiD responses downregulate MYC and IRF4; however, this fails in IMiD-resistant cells. MYC and IRF4 downregulation can also be achieved in IMiD-resistant tumors using inhibitors of BET and EP300 transcriptional coactivator proteins; however, in vivo these drugs have a narrow therapeutic window...
September 28, 2023: Blood cancer discovery
https://read.qxmd.com/read/37662955/impaired-tissue-homing-by-the-ikzf3-n159s-variant-is-mediated-by-interfering-with-ikaros-function
#24
JOURNAL ARTICLE
Jingjie Chang, Motoi Yamashita, Aditya K Padhi, Kam Y J Zhang, Ichiro Taniuchi
AIOLOS, encoded by IKZF3 , is a member of the IKZF family of proteins that plays an important role in regulating late B-cell differentiation. Human individuals heterozygous for the AIOLOS p.N160S variant displayed impaired humoral immune responses as well as impaired B and T cell development. We have previously reported that a mouse strain harboring an Ikzf3N159S allele that corresponds to human IKZF3N160S recapitulated immune-deficient phenotypes, such as impaired B cell development and loss of CD23 expression...
2023: Frontiers in Immunology
https://read.qxmd.com/read/37596276/lenalidomide-derivatives-and-proteolysis-targeting-chimeras-for-controlling-neosubstrate-degradation
#25
JOURNAL ARTICLE
Satoshi Yamanaka, Hirotake Furihata, Yuta Yanagihara, Akihito Taya, Takato Nagasaka, Mai Usui, Koya Nagaoka, Yuki Shoya, Kohei Nishino, Shuhei Yoshida, Hidetaka Kosako, Masaru Tanokura, Takuya Miyakawa, Yuuki Imai, Norio Shibata, Tatsuya Sawasaki
Lenalidomide, an immunomodulatory drug (IMiD), is commonly used as a first-line therapy in many haematological cancers, such as multiple myeloma (MM) and 5q myelodysplastic syndromes (5q MDS), and it functions as a molecular glue for the protein degradation of neosubstrates by CRL4CRBN . Proteolysis-targeting chimeras (PROTACs) using IMiDs with a target protein binder also induce the degradation of target proteins. The targeted protein degradation (TPD) of neosubstrates is crucial for IMiD therapy. However, current IMiDs and IMiD-based PROTACs also break down neosubstrates involved in embryonic development and disease progression...
August 18, 2023: Nature Communications
https://read.qxmd.com/read/37581569/c-fos-is-an-integral-component-of-the-ikzf1-transactivator-complex-and-mediates-lenalidomide-resistance-in-multiple-myeloma
#26
JOURNAL ARTICLE
Naoki Osada, Jiro Kikuchi, Hidekatsu Iha, Hiroshi Yasui, Sho Ikeda, Naoto Takahashi, Yusuke Furukawa
BACKGROUND: The immunomodulatory drug lenalidomide, which is now widely used for the treatment of multiple myeloma (MM), exerts pharmacological action through the ubiquitin-dependent degradation of IKZF1 and subsequent down-regulation of interferon regulatory factor 4 (IRF4), a critical factor for the survival of MM cells. IKZF1 acts principally as a tumour suppressor via transcriptional repression of oncogenes in normal lymphoid lineages. In contrast, IKZF1 activates IRF4 and other oncogenes in MM cells, suggesting the involvement of unknown co-factors in switching the IKZF1 complex from a transcriptional repressor to an activator...
August 2023: Clinical and Translational Medicine
https://read.qxmd.com/read/37550396/specific-subsets-of-urothelial-bladder-carcinoma-infiltrating-t-cells-associated-with-poor-prognosis
#27
JOURNAL ARTICLE
Rui Guo, Luyao Wang, Suhang Bai, Danyue Kang, Wei Zhang, Zhenshan Ding, Tianying Xing, Mingxuan Hao, Youfeng Liang, Binbin Jiao, Guan Zhang, Lu Ying, Ruolan Chen, Xiaoyang Chen, Wenjing Zhang, Jiansong Wang, Chuanxing Wan, Changyuan Yu, Haifeng Wang, Zhao Yang
Comprehensive investigation of tumor-infiltrating lymphocytes in cancer is crucial to explore the effective immunotherapies, but the composition of infiltrating T cells in urothelial bladder carcinoma (UBC) remains elusive. Here, single-cell RNA sequencing (scRNA-seq) were performed on total 30,905 T cells derived from peripheral blood, adjacent normal and tumor tissues from two UBC patients. We identified 18 distinct T cell subsets based on molecular profiles and functional properties. Specifically, exhausted T (TEx ) cells, exhausted NKT (NKTEx ) cells, Ki67+ T cells and B cell-like T (B-T) cells were exclusively enriched in UBC...
August 7, 2023: Scientific Reports
https://read.qxmd.com/read/37404374/glucocorticoid-receptor-mediated-nr1d1-chromatin-circadian-misalignment-in-stress-induced-irritable-bowel-syndrome
#28
JOURNAL ARTICLE
Gen Zheng, Suya Pang, Junbao Wang, Fangyu Wang, Qi Wang, Lili Yang, Mengdie Ji, Dejian Xie, Shengtao Zhu, Yang Chen, Yan Zhou, Gerald A Higgins, John W Wiley, Xiaohua Hou, Rong Lin
Stress-elevated glucocorticoids cause circadian disturbances and gut-brain axis (GBA) disorders, including irritable bowel syndrome (IBS). We hypothesized that the glucocorticoid receptor (GR/NR3C1) might cause chromatin circadian misalignment in the colon epithelium. We observed significantly decreased core circadian gene Nr1d1 in water avoidance stressed (WAS) BALB/c colon epithelium, like in IBS patients. WAS decreased GR binding at the Nr1d1 promoter E-box (enhancer box), and GR could suppress Nr1d1 via this site...
July 21, 2023: IScience
https://read.qxmd.com/read/37401304/identification-of-hub-anoikis-associated-genes-and-risk-signature-in-cutaneous-melanoma
#29
JOURNAL ARTICLE
Y-W He, Q-P Fan, A-L Hua, Q Liu
OBJECTIVE: As one of the most lethal and aggressive cutaneous malignancies, cutaneous melanoma (CM) greatly threatens human health and has long challenged clinicians because of its poor therapeutic response. Anoikis is a newly discovered form of apoptosis that was originally identified in the extracellular matrix (ECM). Recent studies have reported that anoikis is central to cancer metastasis. The aim of this study is to explore the role of anoikis-associated genes in CM. MATERIALS AND METHODS: We identified hub anoikis-associated genes in CM and constructed a risk signature for patients with CM...
June 2023: European Review for Medical and Pharmacological Sciences
https://read.qxmd.com/read/37216868/increased-rna-editing-sites-revealed-as-potential-novel-biomarkers-for-diagnosis-in-primary-sj%C3%A3-gren-s-syndrome
#30
JOURNAL ARTICLE
Xiaobing Wang, Lingxiao Zhu, Senhong Ying, Xin Liao, Junjie Zheng, Zhenwei Liu, Jianxia Gao, Miaomiao Niu, Xin Xu, Zihao Zhou, Huji Xu, Jinyu Wu
BACKGROUND: Transcriptome-wide aberrant RNA editing has been shown to contribute to autoimmune diseases, but its extent and significance in primary Sjögren's syndrome (pSS) are currently poorly understood. METHODS: We systematically characterized the global pattern and clinical relevance of RNA editing in pSS by performing large-scale RNA sequencing of minor salivary gland tissues obtained from 439 pSS patients and 130 non-pSS or healthy controls. FINDINGS: Compared with controls, pSS patients displayed increased global RNA-editing levels, which were significantly correlated and clinically relevant to various immune features in pSS...
May 20, 2023: Journal of Autoimmunity
https://read.qxmd.com/read/37066279/photoswitchable-molecular-glues-enable-optical-control-of-transcription-factor-degradation
#31
Christopher J Arp, Martin Reynders, Vedagopuram Sreekanth, Praveen Kokkonda, Michele Pagano, Amit Choudhary, Dirk Trauner
Immunomodulatory drugs (IMiDs), which include thalidomide and its derivatives, have emerged as the standard of care against multiple myeloma. They function as molecular glues that bind to the E3 ligase cereblon (CRBN) and induce protein interactions with neosubstrates, including the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). The subsequent ubiquitylation and degradation of these transcription factors underlies the antiproliferative activity of IMiDs. Here, we introduce photoswitchable immunomodulatory drugs (PHOIMiDs) that can be used to degrade Ikaros and Aiolos in a light-dependent fashion...
April 9, 2023: bioRxiv
https://read.qxmd.com/read/37037192/on-ternary-complex-stability-in-protein-degradation-in-silico-molecular-glue-binding-affinity-calculations
#32
JOURNAL ARTICLE
Dahlia R Weiss, Andrea Bortolato, Yongnian Sun, Xianmei Cai, Chon Lai, Sixuan Guo, Lihong Shi, Veerabahu Shanmugasundaram
Molecular glues are small molecules that simultaneously bind to two proteins, creating a chemically induced protein-protein interface. CELMoDs (cereblon E3 ligase modulators) are a class of molecular glues that promote recruitment of neosubstrate proteins to the E3 ubiquitin ligase cereblon (CRBN) for poly-Lys48-ubiquitination and proteasomal degradation. Ternary complex structures of clinical CELMoDs CC-885 and CC-90009 bound to CRBN and neosubstrate G1 to S phase transition protein 1 (GSPT1) have been experimentally determined...
April 10, 2023: Journal of Chemical Information and Modeling
https://read.qxmd.com/read/36967927/the-multi-omics-analysis-identifies-a-novel-cuproptosis-anoikis-related-gene-signature-in-prognosis-and-immune-infiltration-characterization-of-lung-adenocarcinoma
#33
JOURNAL ARTICLE
Guanyu Jiang, Chenghu Song, Xiaokun Wang, Yongrui Xu, Huixing Li, Zhao He, Ying Cai, Mingfeng Zheng, Wenjun Mao
BACKGROUND: Lung adenocarcinoma (LUAD) has emerged as one of the most aggressive lethal cancers. Anoikis serves as programmed apoptosis initiated by the detachment of cells from the extracel-lular matrix. Cuproptosis is distinct from traditional cell death modalities. The above two modes are both closely related to tumor progression, prognosis, and treatment. However, whether they have synergistic effects in LUAD deserves further investigation. METHODS: The anoikis-related prognostic genes (ANRGs) co-expressed with cuproptosis-associated genes (CAGs) were screened using correlation analysis, analysis of variance, least absolute shrinkage, and selection operator (LASSO), and COX regression followed by functional analysis, and then LUAD risk score model was constructed...
March 2023: Heliyon
https://read.qxmd.com/read/36967681/association-of-asthma-risk-alleles-with-acute-respiratory-tract-infections-and-wheezing-illnesses-in-young-children
#34
JOURNAL ARTICLE
Ville Forsström, Laura Toivonen, Kiara Homil, Matti Waris, Casper-Emil T Pedersen, Klaus Bønnelykke, Tuomas Jartti, Ville Peltola
BACKGROUND: Genome-wide association studies have identified several risk alleles for early childhood asthma, particularly in the 17q21 locus and in the cadherin-related family member 3 (CDHR3) gene. Contribution of these alleles to the risk of acute respiratory tract infections (ARI) in the early childhood is unclear. METHODS: We analyzed data from the STEPS birth-cohort study of unselected children and the VINKU and VINKU2 studies on children with severe wheezing illness...
March 27, 2023: Journal of Infectious Diseases
https://read.qxmd.com/read/36930079/ikzf3-is-a-novel-prognostic-biomarker-for-head-and-neck-squamous-cell-carcinoma-a-study-based-on-bioinformatics-analysis
#35
JOURNAL ARTICLE
Hongxiang Li, Mengmeng Ye, Zeyang Hu, Haoxuan Lu, Dawei Zheng, Mi Wu, Ting Ge, Shuguang Xu, Zhen Ge, Shuoni Zhang, Guodong Xu, Hang Chen
In the past few years, immunotherapy of tumors has become an extensive research hotspot, and the value of IKZF family genes in the tumor microenvironment has also been increasingly recognized. However, the expression of the IKAROS family zinc finger 3 (IKZF3) gene in human head and neck squamous cell carcinoma (HNSCC) and its prognostic value were not reported for the main subset until now. In the present study, we analyzed the relationship between IKZF3 gene expression and the survival of HNSCC patients. To evaluate the potential of IKZF3 as a prognostic biomarker for HNSCC comprehensively, multiple online analysis tools, including UALCAN, cBioPortal, GEPIA, WebGestalt, String, Genomic Data Commons, and TIMER databases were utilized in our study...
March 17, 2023: Medicine (Baltimore)
https://read.qxmd.com/read/36928053/-not-available
#36
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
2023: Arerugī, [Allergy]
https://read.qxmd.com/read/36762574/disentangling-the-common-genetic-architecture-and-causality-of-rheumatoid-arthritis-and-systemic-lupus-erythematosus-with-covid-19-outcomes-genome-wide-cross-trait-analysis-and-bi-directional-mendelian-randomization-study
#37
JOURNAL ARTICLE
Minhao Yao, Xin Huang, Yunshan Guo, Jie V Zhao, Zhonghua Liu
PURPOSE: COVID-19 may cause a dysregulation of the immune system and has complex relationships with multiple autoimmune diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, little is known about their common genetic architecture. METHODS: Using the latest data from COVID-19 host genetics consortium and consortia on RA and SLE, we conducted a genome-wide cross-trait analysis to examine the shared genetic etiology between COVID-19 and RA/SLE and evaluated their causal associations using bi-directional Mendelian randomization...
February 10, 2023: Journal of Medical Virology
https://read.qxmd.com/read/36755810/chromatin-regulator-related-gene-signature-for-predicting-prognosis-and-immunotherapy-efficacy-in-breast-cancer
#38
JOURNAL ARTICLE
Dongxu Feng, Wenbing Li, Wei Wu, Ulf Dietrich Kahlert, Pingfa Gao, Gangfeng Hu, Xia Huang, Wenjie Shi, Huichao Li
BACKGROUND: Many studies have found that chromatin regulators (CRs) are correlated with tumorigenesis and disease prognosis. Here, we attempted to build a new CR-related gene model to predict breast cancer (BC) survival status. METHODS: First, the CR-related differentially expressed genes (DEGs) were screened in normal and tumor breast tissues, and the potential mechanism of CR-related DEGs was determined by function analysis. Based on the prognostic DEGs, the Cox regression model was applied to build a signature for BC...
2023: Journal of Oncology
https://read.qxmd.com/read/36709169/-in-vitro-pharmacodynamic-studies-of-novel-class-%C3%A2-and-%C3%A2-b-selective-histone-deacetylase-inhibitor-purinostat-mesylate-in-the-treatment-of-diffuse-large-b-cell-lymphoma-and-its-mechanism
#39
JOURNAL ARTICLE
J Wang, A L Zhao, H Li, L Y Yang, L J Chen, T Niu
Objective: To investigate the in vitro inhibitory activity of a novel class Ⅰ and Ⅱb selective histone deacetylase (HDAC) inhibitor, purinostat mesylate (PM) , in diffuse large B-cell lymphoma and its mechanism. Methods: The 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide method was used to detect the effect of PM on cell proliferation. The effects of PM on cell cycle and apoptosis were detected by flow cytometry. The acetylation levels of HDAC substrate, cell cycle protein, apoptosis-related protein, and oncogene protein expression were detected by Western blot...
September 14, 2022: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://read.qxmd.com/read/36696464/btk-and-plcg2-remain-unmutated-in-one-third-of-patients-with-cll-relapsing-on-ibrutinib
#40
JOURNAL ARTICLE
Silvia Bonfiglio, Lesley-Ann Sutton, Viktor Ljungström, Antonella Capasso, Tatjana Pandzic, Simone Weström, Hassan Foroughi-Asl, Aron Skaftason, Anna Gellerbring, Anna Lyander, Francesca Gandini, Gianluca Gaidano, Livio Trentin, Lisa Bonello, Gianluigi Reda, Csaba Bödör, Niki Stavroyianni, Constantine S Tam, Roberto Marasca, Francesco Forconi, Panayiotis Panayiotidis, Ingo Ringshausen, Ozren Jaksic, Anna Maria Frustaci, Sunil Iyengar, Marta Coscia, Stephen P Mulligan, Loïc Ysebaert, Vladimir Strugov, Carolina Pavlovsky, Renata Walewska, Anders Österborg, Diego Cortese, Pamela Ranghetti, Panagiotis Baliakas, Kostas Stamatopoulos, Lydia Scarfò, Richard Rosenquist, Paolo Ghia
Patients with chronic lymphocytic leukemia (CLL) progressing on ibrutinib constitute an unmet clinical need. Though BTK and PLCG2 mutations are associated with ibrutinib resistance, their frequency and relevance to progression are not fully understood. In this multicenter retrospective observational study, we analyzed 98 patients with CLL treated with ibrutinib (49 relapsing after an initial response and 49 still responding after ≥1 year of continuous treatment) using a next-generation sequencing (NGS) panel (1% sensitivity) comprising 13 CLL-relevant genes including BTK and PLCG2...
January 25, 2023: Blood Advances
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