keyword
https://read.qxmd.com/read/38421303/kdm4c-promotes-mouse-hippocampal-neural-stem-cell-proliferation-through-modulating-apoe-expression
#1
JOURNAL ARTICLE
Kun Zhu, Hanyue Zhang, Yan Luan, Baoqi Hu, Tu Shen, Bo Ma, Zhichao Zhang, Xiaoyan Zheng
KDM4C is implicated in the regulation of cell proliferation, differentiation, and maintenance in various stem cell types. However, its function in neural stem cells (NSCs) remains poorly understood. Therefore, this study aims to investigate the role and regulatory mechanism of KDM4C in NSCs. Primary hippocampal NSCs were isolated from neonatal mice, and both in vivo and in vitro lentivirus-mediated overexpression of KDM4C were induced in these hippocampal NSCs. Staining results revealed a significant increase in BrdU- and Ki-67-positive cells, along with an elevated number of cells in S phases due to KDM4C overexpression...
March 15, 2024: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/37848946/kdm4c-mediated-senescence-defense-is-a-targetable-vulnerability-in-gastric-cancer-harboring-tp53-mutations
#2
JOURNAL ARTICLE
Kaiqing Wang, Zhicheng Gong, Yanyan Chen, Meimei Zhang, Suzeng Wang, Surui Yao, Zhihui Liu, Zhaohui Huang, Bojian Fei
BACKGROUND: Gastric cancer patients harboring a TP53 mutation exhibit a more aggressive and chemoresistant phenotype. Unfortunately, efforts to identify the vulnerabilities to overcome these aggressive malignancies have made minimal progress in recent years. Therefore, there is an urgent need to explore the novel therapeutic strategies for this subclass. Histone methylation modulators are critical epigenetic targets for cancer therapies that help maintain the malignancies of cancers harboring TP53 mutations and senescence evasion...
October 17, 2023: Clinical Epigenetics
https://read.qxmd.com/read/37767575/twist-family-bhlh-transcription-factor-1-is-required-for-the-maintenance-of-leukemia-stem-cell-in-mll-af9-acute-myeloid-leukemia
#3
JOURNAL ARTICLE
Nan Wang, Jing Yin, Na You, Wenqi Zhu, Nini Guo, Xiaoyan Liu, Peiwen Zhang, Wanling Huang, Yueqiao Xie, Qian Ren, Xiaotong Ma
Leukemia stem cells (LSCs) are a rare population capable of limitless self-renewal and are responsible for the initiation, maintenance, and relapse of leukemia. Elucidation of the mechanisms underlying the regulation of LSC function could provide novel treatment strategies. Here, we show that TWIST1 is extremely highly expressed in the LSCs of MLL-AF9+ acute myeloid leukemia (AML), and its upregulation is positively regulated by KDM4C in an H3K9me3 demethylation-dependent manner. We further demonstrate that TWIST1 is essential for the viability, dormancy, and self-renewal capacities of LSCs, and it promotes the initiation and maintenance of MLL-AF9-mediated AML...
September 28, 2023: Haematologica
https://read.qxmd.com/read/37731134/identification-of-single-nucleotide-polymorphisms-snps-associated-with-chronic-graft-versus-host-disease-in-patients-undergoing-allogeneic-hematopoietic-cell-transplantation
#4
MULTICENTER STUDY
Jean-Luc C Mougeot, Micaela F Beckman, Allan J Hovan, Bengt Hasséus, Karin Garming Legert, Jan-Erik Johansson, Inger von Bültzingslöwen, Michael T Brennan, Farah Bahrani Mougeot
INTRODUCTION: Chronic graft-versus-host disease (cGVHD) is a debilitating side effect of allogeneic hematopoietic cell transplantation (HCT), affecting the quality of life of patients. We used whole exome sequencing to identify candidate SNPs and complete a multi-marker gene-level analysis using a cohort of cGVHD( +) (N = 16) and cGVHD( -) (N = 66) HCT patients. METHODS: Saliva samples were collected from HCT patients (N = 82) pre-conditioning in a multi-center study from March 2011 to May 2018...
September 21, 2023: Supportive Care in Cancer
https://read.qxmd.com/read/37443959/genome-wide-association-analysis-of-muscle-ph-in-texel-sheep-%C3%A3-altay-sheep-f-2-resource-population
#5
JOURNAL ARTICLE
Yilong Zhao, Sangang He, Jinfeng Huang, Mingjun Liu
pH was one of the important meat quality traits, which was an important factor affecting the storage/shelf life and quality of meat in meat production. In order to find a way to extend the storage/shelf life, the pH values (pH45min , pH24h , pH48h and pH72h ) of the longissimus dorsi muscles in F2 individuals of 462 Texel sheep × Altay sheep were determined, genotyping was performed using Illumina Ovine SNP 600 K BeadChip and whole genome resequencing technology, a genome-wide association analysis (GWAS) was used to screen the candidate genes and molecular markers for pH values related to the quality traits of mutton, and the effects of population stratification were detected by Q-Q plots...
June 30, 2023: Animals: An Open Access Journal From MDPI
https://read.qxmd.com/read/37286866/the-role-of-histone-h3-lysine-demethylases-in-glioblastoma
#6
REVIEW
Dejauwne Young, Chandan Guha, Simone Sidoli
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults with an average survival of 15-18 months. Part of its malignancy derives from epigenetic regulation that occurs as the tumor develops and after therapeutic treatment. Specifically, enzymes involved in removing methylations from histone proteins on chromatin, i.e., lysine demethylases (KDMs), have a significant impact on GBM biology and reoccurrence. This knowledge has paved the way to considering KDMs as potential targets for GBM treatment...
June 8, 2023: Cancer Metastasis Reviews
https://read.qxmd.com/read/37161649/bach1-encourages-ferroptosis-by-activating-kdm4c-mediated-cox2-demethylation-after-cerebral-ischemia-reperfusion-injury
#7
JOURNAL ARTICLE
Tianqi Zhang, Meimei Yang, Chi Ma, Xinya Wei, Zhuobo Zhang
It has been confirmed that BTB domain and CNC homolog 1 (BACH1) are involved in ferroptosis related diseases. However, the function of BACH1 in cerebral ischemia-reperfusion injury (CIRI) induced ferroptosis remains to be largely unrevealed. Firstly, analysis of differentially expressed genes (DEGs) in CIRI based on the GEO dataset GSE119121 revealed that BACH1 was upregulated in CIRI. BACH1 level was prominently increased in MCAO/reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) cell model...
May 9, 2023: European Journal of Neuroscience
https://read.qxmd.com/read/37117173/kdm4c-silencing-inhibits-cell-migration-and-enhances-radiosensitivity-by-inducing-cxcl2-transcription-in-hepatocellular-carcinoma
#8
JOURNAL ARTICLE
Zhen Zeng, Zixuan Li, Jun Xue, Huichan Xue, Zhiwei Liu, Wenxuan Zhang, Hongli Liu, Shuangbing Xu
KDM4C, which is a histone lysine demethylase, has been proposed to participate in the malignant transformation and progression of several types of cancer. However, its roles in hepatocellular carcinoma (HCC) remain poorly understood. Here, we find that KDM4C protein expression is increased in HCC and promotes HCC cell growth, proliferation and migration. Furthermore, we provide evidence that depletion of KDM4C leads to a defective G2/M checkpoint, increases radiation-induced DNA damage, impairs DNA repair and enhances radiosensitivity in HCC cells...
April 28, 2023: Cell Death Discovery
https://read.qxmd.com/read/36990534/multi-cpg-linear-regression-models-to-accurately-predict-paclitaxel-and-docetaxel-activity-in-cancer-cell-lines
#9
REVIEW
Manny D Bacolod, Paul B Fisher, Francis Barany
The microtubule-targeting paclitaxel (PTX) and docetaxel (DTX) are widely used chemotherapeutic agents. However, the dysregulation of apoptotic processes, microtubule-binding proteins, and multi-drug resistance efflux and influx proteins can alter the efficacy of taxane drugs. In this review, we have created multi-CpG linear regression models to predict the activities of PTX and DTX drugs through the integration of publicly available pharmacological and genome-wide molecular profiling datasets generated using hundreds of cancer cell lines of diverse tissue of origin...
2023: Advances in Cancer Research
https://read.qxmd.com/read/36804120/luteolin-directly-binds-to-kdm4c-and-attenuates-ovarian-cancer-stemness-via-epigenetic-suppression-of-ppp2ca-yap-axis
#10
JOURNAL ARTICLE
Yunzhe Li, Yunran Hu, Lingling Yang, Jingshu Liu, Chenxi Cui, Muyao Yang, Dongling Zou, Lei Zhou, Qi Zhou, Weihong Ge, Tingyuan Lang
Long-term use of low-toxic natural products holds the promise for eradicating cancer stem cells. In this study, we report that luteolin, a natural flavonoid, attenuates the stemness of ovarian cancer stem cells (OCSCs) by directly binding to KDM4C and epigenetic suppression of PPP2CA/YAP axis. Ovarian cancer stem like cells (OCSLCs) isolated by suspension culture and CD133 + ALDH+ cell sorting was employed as OCSCs model. The maximal non-toxic dose of luteolin suppressed stemness properties, including sphere-forming capacity, the expression of OCSCs markers, sphere-initiating and tumor-initiating capacities, as well as the percentage of CD133 + ALDH+ cells of OCSLCs...
February 16, 2023: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/36651250/-expression-pattern-of-the-histone-lysine-demethylase-family-and-its-potential-role-in-bladder-cancer-a-multi-omics-analysis
#11
JOURNAL ARTICLE
X Fu, G Yu, Y Guo
OBJECTIVE: To investigate the expression patterns of 19 histone lysine demethylases (KDMs) and their role in bladder cancer. METHODS: In this study, UALCAN and GSCALite were used to analyze the transcriptional expression, methylation level and somatic variation of KDMs in bladder cancer samples from TCGA. Kaplan Meier-Plotter and Assistant for clinical bioinformatics were used to investigate the effect of KDMs expression on the prognosis of BLCA samples. The immune infiltration and drug sensitivity of KDMs in bladder cancer were analyzed by Timer and GSCALite...
December 20, 2022: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://read.qxmd.com/read/36012577/essential-roles-of-the-histone-demethylase-kdm4c-in-renal-development-and-acute-kidney-injury
#12
JOURNAL ARTICLE
Heng-Chih Pan, Yau-Hung Chen, Wei-Ching Fang, Vin-Cent Wu, Chiao-Yin Sun
BACKGROUND: Lysine demethylase 4C (KDM4C) is a nuclear protein that is essential for histone modification and acts as an important regulator of several transcription factors. Previous studies have shown that KDM4C may also play a role in mediating stress responses. The purpose of this study was to examine the roles of KDM4C in kidney development and acute kidney injury (AKI). METHODS: The effect of KDM4C on kidney development was assessed by comparing the kidney phenotype between 96 zebrafish embryos treated with kdm4c-morpholino oligonucleotide and 96 untreated zebrafish embryos...
August 18, 2022: International Journal of Molecular Sciences
https://read.qxmd.com/read/35886932/kdm4c-contributes-to-trophoblast-like-stem-cell-conversion-from-porcine-induced-pluripotent-stem-cells-pipscs-via-regulating-cdx2
#13
JOURNAL ARTICLE
Shuai Yu, Qiaoyan Shen, Rui Zhang, Xiaolong Wu, Juqing Zhang, Wenxu Zhao, Xiaojie Wu, Na Li, Sha Peng, Shiqiang Zhang, Fan Yang, Jinlian Hua
Studies on ESRRB-regulating porcine-induced pluripotent stem cells (piPSCs) converted to trophoblast-like stem cells (TLSCs) contribute to the understanding of early embryo development. However, the epigenetic modification regulation network during the conversion is poorly understood. Here, the global change in histone H3 Lysine 4, 9, 27, 36 methylation and Lysine 27 acetylation was investigated in piPSCs and TLSCs. We found a high modification profile of H3K36me2 in TLSCs compared to that of piPSCs, whereas the profiles of other modifications remained constant...
July 8, 2022: International Journal of Molecular Sciences
https://read.qxmd.com/read/35883846/demethylation-of-h3k9-and-h3k27-contributes-to-the-tubular-renal-damage-triggered-by-endoplasmic-reticulum-stress
#14
JOURNAL ARTICLE
Paula Diaz-Bulnes, Maria Laura Saiz, Viviana Corte-Iglesias, Raúl R Rodrigues-Diez, Aida Bernardo Florez, Cristian Ruiz Bernet, Cristina Martin Martin, Marta Ruiz-Ortega, Beatriz Suarez-Alvarez, Carlos López-Larrea
Loss of protein homeostasis (proteostasis) in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR), restoring correct protein folding. Sustained ER stress exacerbates activation of the major UPR branches (IRE1α/XBP1, PERK/ATF4, ATF6), inducing expression of numerous genes involved in inflammation, cell death, autophagy, and oxidative stress. We investigated whether epigenetic dynamics mediated by histone H3K9 and H3K27 methylation might help to reduce or inhibit the exacerbated and maladaptive UPR triggered in tubular epithelial cells...
July 12, 2022: Antioxidants (Basel, Switzerland)
https://read.qxmd.com/read/35871166/exosomal-circpabpc1-promotes-colorectal-cancer-liver-metastases-by-regulating-hmga2-in-the-nucleus-and-bmp4-adam19-in-the-cytoplasm
#15
JOURNAL ARTICLE
Yang Li, Jialei Hu, Meng Wang, Yihang Yuan, Fangyuan Zhou, Haosen Zhao, Tianming Qiu, Leilei Liang
Liver metastasis is the leading cause of death in colorectal carcinoma (CRC). However, little is known about the mechanisms of transferring effector messages between the primary tumor and the site of metastasis. Exosomes provide a novel transfer message method, and exosomal circular RNAs (circRNAs) play critical regulatory roles in cancer biology. In this study, the results showed that the expression of circPABPC1 was aberrantly upregulated in CRC tissues and exosomes. Exosomal circPABPC1 was considered an oncogene by functional experimental analysis in vitro and in vivo...
July 23, 2022: Cell Death Discovery
https://read.qxmd.com/read/35654819/histone-demethylase-kdm4c-is-a-functional-dependency-in-jak2-mutated-neoplasms
#16
JOURNAL ARTICLE
Philipp Ernst, Tina M Schnöder, Nicolas Huber, Florian Perner, Ashok Kumar Jayavelu, Theresa Eifert, Chen-Jen Hsu, Nuria Tubío-Santamaría, Carl C Crodel, Martin Ungelenk, Christian A Hübner, Joachim H Clement, Andreas Hochhaus, Florian H Heidel
Mutations of the JAK2 gene are frequent aberrations in the aging hematopoietic system and in myeloid neoplasms. While JAK-inhibitors efficiently reduce hyperinflammation induced by the constitutively active mutated JAK2 kinase, the malignant clone and abundance of mutated cells remains rather unaffected. Here, we sought to assess for genetic vulnerabilities of JAK2-mutated clones. We identified lysine-specific demethylase KDM4C as a selective genetic dependency that persists upon JAK-inhibitor treatment. Genetic inactivation of KDM4C in human and murine JAK2-mutated cells resulted in loss of cell competition and reduced proliferation...
July 2022: Leukemia
https://read.qxmd.com/read/35633893/nephrotoxicity-of-perfluorooctane-sulfonate-pfos-effect-on-transcription-and-epigenetic-factors
#17
JOURNAL ARTICLE
Yi Wen, Faizan Rashid, Zeeshan Fazal, Ratnakar Singh, Michael J Spinella, Joseph Irudayaraj
Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in nephrotoxicity with altered metabolism, carcinogenesis, and fibrosis potential. We studied the underlying epigenetic mechanism involving transcription factors of PFOS-induced kidney injury. A 14-day orally dosed mouse model was chosen to study acute influences in vivo . Messenger RNA expression analysis and gene set enrichment analysis were performed to elucidate the relationship between epigenetic regulators, transcription factors, kidney disease, and metabolism homeostasis...
2022: Environmental Epigenetics
https://read.qxmd.com/read/35534851/natural-product-myricetin-is-a-pan-kdm4-inhibitor-which-with-poly-lactic-co-glycolic-acid-formulation-effectively-targets-castration-resistant-prostate-cancer
#18
JOURNAL ARTICLE
Jai-Shin Liu, Wei-Kai Fang, Shan-Min Yang, Meng-Chen Wu, Tsan-Jan Chen, Chih-Ming Chen, Tung-Yueh Lin, Kai-Lun Liu, Chien-Ming Wu, Yun-Ching Chen, Chih-Pin Chuu, Ling-Yu Wang, Hsing-Pang Hsieh, Hsing-Jien Kung, Wen-Ching Wang
BACKGROUND: Castration-resistant prostate cancer (CRPC) with sustained androgen receptor (AR) signaling remains a critical clinical challenge, despite androgen depletion therapy. The Jumonji C-containing histone lysine demethylase family 4 (KDM4) members, KDM4A‒KDM4C, serve as critical coactivators of AR to promote tumor growth in prostate cancer and are candidate therapeutic targets to overcome AR mutations/alterations-mediated resistance in CRPC. METHODS: In this study, using a structure-based approach, we identified a natural product, myricetin, able to block the demethylation of histone 3 lysine 9 trimethylation by KDM4 members and evaluated its effects on CRPC...
May 9, 2022: Journal of Biomedical Science
https://read.qxmd.com/read/35522148/focal-structural-variants-revealed-by-whole-genome-sequencing-disrupt-the-histone-demethylase-kdm4c-in-b-cell-lymphomas
#19
JOURNAL ARTICLE
Cristina Lopez, Nikolai Schleussner, Stephan H Bernhart, Kortine Kleinheinz, Stephanie Sungalee, Henrike L Sczakiel, Helene Kretzmer, Umut H Toprak, Selina Glaser, Rabea Wagener, Ole Ammerpohl, Susanne Bens, Maciej Giefing, Juan C Gonzalez Sanchez, Gordana Apic, Daniel Hubschmann, Martin Janz, Markus Kreuz, Anja Mottok, Judith M Muller, Julian Seufert, Steve Hoffmann, Jan O Korbel, Robert B Russell, Roland Schule, Lorenz Trumper, Wolfram Klapper, Bernhard Radlwimmer, Peter Lichter, Ralf Kuppers, Matthias Schlesner, Stephan Mathas, Reiner Siebert
Histone methylation-modifiers, like EZH2 and KMT2D, are recurrently altered in B-cell lymphomas. To comprehensively describe the landscape of alterations affecting genes encoding histone methylation-modifiers in lymphomagenesis we investigated whole genome and transcriptome data of 186 mature B-cell lymphomas sequenced in the ICGC MMML-Seq project. Besides confirming common alterations of KMT2D (47% of cases), EZH2 (17%), SETD1B (5%), PRDM9 (4%), KMT2C (4%), and SETD2 (4%) also identified by prior exome or RNAseq studies, we here unravel KDM4C in chromosome 9p24, encoding a histone demethylase, to be recurrently altered...
April 28, 2022: Haematologica
https://read.qxmd.com/read/35484653/kdm4c-in-gc-lymphoma-a-new-piece-of-the-epigenetic-puzzle
#20
JOURNAL ARTICLE
Karina Close, Jude Fitzgibbon
Not available.
April 28, 2022: Haematologica
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