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https://www.readbyqxmd.com/read/29042072/mir-200b-downregulates-kruppel-like-factor-2-klf2-during-acute-hypoxia-in-human-endothelial-cells
#1
Rafal Bartoszewski, Marcin Serocki, Anna Janaszak-Jasiecka, Sylwia Bartoszewska, Kinga Kochan-Jamrozy, Arkadiusz Piotrowski, Jarosław Króliczewski, James F Collawn
The role of microRNAs in controlling angiogenesis is recognized as a promising therapeutic target in both cancer and cardiovascular disorders. However, understanding a miRNA's pleiotropic effects on angiogenesis is a limiting factor for these types of therapeutic approaches. Using genome-wide next-generation sequencing, we examined the role of an antiangiogenic miRNA, miR-200b, in primary human endothelial cells. The results indicate that miR-200b has complex effects on hypoxia-induced angiogenesis in human endothelia and importantly, that many of the reported miR-200b effects using miRNA overexpression may not be representative of the physiological role of this miRNA...
October 13, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29036642/striking-a-balance-regulation-of-transposable-elements-by-zfp281-and-mll2-in-mouse-embryonic-stem-cells
#2
Qian Dai, Yang Shen, Yan Wang, Xin Wang, Joel Celio Francisco, Zhuojuan Luo, Chengqi Lin
Transposable elements (TEs) compose about 40% of the murine genome. Retrotransposition of active TEs such as LINE-1 (L1) tremendously impacts genetic diversification and genome stability. Therefore, transcription and transposition activities of retrotransposons are tightly controlled. Here, we show that the Krüppel-like zinc finger protein Zfp281 directly binds and suppresses a subset of retrotransposons, including the active young L1 repeat elements, in mouse embryonic stem (ES) cells. In addition, we find that Zfp281-regulated L1s are highly enriched for 5-hydroxymethylcytosine (5hmC) and H3K4me3...
September 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29030550/a-conserved-klf-autophagy-pathway-modulates-nematode-lifespan-and-mammalian-age-associated-vascular-dysfunction
#3
Paishiun N Hsieh, Guangjin Zhou, Yiyuan Yuan, Rongli Zhang, Domenick A Prosdocimo, Panjamaporn Sangwung, Anna H Borton, Evgenii Boriushkin, Anne Hamik, Hisashi Fujioka, Ciaran E Fealy, John P Kirwan, Maureen Peters, Yuan Lu, Xudong Liao, Diana Ramírez-Bergeron, Zhaoyang Feng, Mukesh K Jain
Loss of protein and organelle quality control secondary to reduced autophagy is a hallmark of aging. However, the physiologic and molecular regulation of autophagy in long-lived organisms remains incompletely understood. Here we show that the Kruppel-like family of transcription factors are important regulators of autophagy and healthspan in C. elegans, and also modulate mammalian vascular age-associated phenotypes. Kruppel-like family of transcription factor deficiency attenuates autophagy and lifespan extension across mechanistically distinct longevity nematode models...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29023738/klf2-mediates-enhanced-chemoreflex-sensitivity-disordered-breathing-and-autonomic-dysregulation-in-heart-failure
#4
Noah J Marcus, Rodrigo Del Rio, Yanfeng Ding, Harold D Schultz
KEY POINTS: Enhanced carotid body chemoreflex activity contributes to development of disordered breathing patterns, autonomic dysregulation and increases in incidence of arrhythmia in animal models of reduced ejection fraction heart failure. Chronic reductions in carotid artery blood flow are associated with increased carotid body chemoreceptor activity. Krüppel-like Factor 2 (KLF2) is a shear stress-sensitive transcription factor that regulates the expression of enzymes which have previously been shown to play a role in increased chemoreflex sensitivity...
September 6, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29017567/impairment-of-igf2-gene-expression-in-prostate-cancer-is-triggered-by-epigenetic-dysregulation-of-igf2-dmr0-and-its-interaction-with-klf4
#5
Undraga Schagdarsurengin, Angela Lammert, Natalie Schunk, Diana Sheridan, Stefan Gattenloehner, Klaus Steger, Florian Wagenlehner, Temuujin Dansranjavin
BACKGROUND: Human cancer cells often exhibit impaired IGF2 expression and the underlying mechanisms are multifaceted and complex. Besides the well-known imprinting control region IGF2/H19-ICR, the involvement of a differentially methylated region in the promoter P0 of IGF2 gene (IGF2-DMR0) has been suggested. Here, we evaluate several mechanisms potentially leading to up- and/or down-regulation of IGF2 expression in prostate cancer and present a novel role of Kruppel-like factor 4 (KLF4) as a transcriptional regulator of IGF2 binding in IGF2-DMR0...
October 10, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28992202/kr%C3%A3-ppel-like-factors-and-vascular-wall-homeostasis
#6
Yanbo Fan, Haocheng Lu, Wenying Liang, Wenting Hu, Jifeng Zhang, Y Eugene Chen
Cardiovascular diseases (CVDs) are major causes of death worldwide. Identification of promising targets for prevention and treatment of CVDs is paramount in the cardiovascular field. Numerous transcription factors regulate cellular function through modulation of specific genes and thereby are involved in the physiological and pathophysiological processes of CVDs. Although Krüppel-like factors (KLFs) have a similar protein structure with a conserved zinc finger domain, they possess distinct tissue and cell distribution patterns as well as biological functions...
August 23, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28988130/klf4-overcomes-tamoxifen-resistance-by-suppressing-mapk-signaling-pathway-and-predicts-good-prognosis-in-breast-cancer
#7
Yunlu Jia, Jichun Zhou, Xiao Luo, Miao Chen, Yongxia Chen, Ji Wang, Hanchu Xiong, Xiaogang Ying, Wenxian Hu, Wenhe Zhao, Wuguo Deng, Linbo Wang
Tamoxifen resistance represents a daunting challenge to the successful treatment for breast cancer. Krüppel-like factor 4 has critical roles in the development and progression of breast cancer, but its expression, function and regulation in the efficacy of TAM therapy in breast cancer have yet to be investigated. Here, we examined the clinical significance and biologic effects of KLF4 in breast cancer. Firstly, higher expression of KLF4 correlated with increased TAM sensitivity in breast cancer cells, and analysis of GEO datasets indicated that KLF4 expression was positively correlated with ERα and enhanced expression of KLF4 sensitized breast cancer patients to endocrine therapy...
October 4, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28986741/kr%C3%A3-ppel-like-factor-8-overexpression-correlates-with-poor-prognosis-in-non-small-cell-lung-cancer
#8
Jianchao Li, Yifei Liu, Jianhua Xue, Mingming Xu, Jianguo Zhang, Junhua Liu, Wenyi Wang
Krüppel-like factor 8 (KLF8) plays a key role in cancer progression. However, its expression pattern and relationship with clinicopathological characteristics in non-small cell lung cancer (NSCLC) has not been completely elucidated. The study aimed to investigate the expression of KLF8 and its correlation with clinical pathologic features in NSCLC and to explore the potential mechanism. The expression of KLF8 in NSCLC was detected by RT-PCR, Western blot and immunohistochemistry. The expression of Vimentin and E-cadherin, epithelial-mesenchymal transition (EMT) markers, were detected by immunohistochemistry in the NSCLC...
October 6, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28985359/parp1-controls-klf4-mediated-telomerase-expression-in-stem-cells-and-cancer-cells
#9
Meng-Hsun Hsieh, Yi-Ting Chen, You-Tzung Chen, Yi-Hsuan Lee, Jean Lu, Chung-Liang Chien, Hsin-Fu Chen, Hong-Nerng Ho, Chia-Jung Yu, Zhao-Qi Wang, Shu-Chun Teng
Telomerase is highly expressed in cancer and embryonic stem cells (ESCs) and implicated in controlling genome integrity, cancer formation and stemness. Previous studies identified that Krüppel-like transcription factor 4 (KLF4) activates telomerase reverse transcriptase (TERT) expression and contributes to the maintenance of self-renewal in ESCs. However, little is known about how KLF4 regulates TERT expression. Here, we discover poly(ADP-ribose) polymerase 1 (PARP1) as a novel KLF4-interacting partner. Knockdown of PARP1 reduces TERT expression and telomerase activity not only in cancer cells, but also in human and mouse ESCs...
August 1, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28983631/integrated-analysis-reveals-candidate-genes-and-transcription-factors-in-lung-adenocarcinoma
#10
Baiwang Chen, Shuhong Gao, Changwei Ji, Ge Song
Lung adenocarcinoma is the most common type of non‑small cell lung cancer in Asia. Therefore, it is important to improve understanding of the underlying transcriptional regulatory mechanisms involved. The present study aimed to identify potential candidate genes and transcription factors (TFs) associated with the disease. Four gene expression profiles were downloaded from the Gene Expression Omnibus database, which included 141 lung adenocarcinoma patients and 191 healthy controls. The differentially expressed genes (DEGs) were screened out and functional annotation was performed...
September 28, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28982762/a-dynamic-interplay-of-enhancer-elements-regulates-klf4-expression-in-na%C3%A3-ve-pluripotency
#11
Liangqi Xie, Sharon E Torigoe, Jifang Xiao, Daniel H Mai, Li Li, Fred P Davis, Peng Dong, Herve Marie-Nelly, Jonathan Grimm, Luke Lavis, Xavier Darzacq, Claudia Cattoglio, Zhe Liu, Robert Tjian
Transcription factor (TF)-directed enhanceosome assembly constitutes a fundamental regulatory mechanism driving spatiotemporal gene expression programs during animal development. Despite decades of study, we know little about the dynamics or order of events animating TF assembly at cis-regulatory elements in living cells and the long-range molecular "dialog" between enhancers and promoters. Here, combining genetic, genomic, and imaging approaches, we characterize a complex long-range enhancer cluster governing Krüppel-like factor 4 (Klf4) expression in naïve pluripotency...
September 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28978525/ampk-klf2-signaling-pathway-mediates-the-proangiogenic-effect-of-erythropoietin-in-endothelial-colony-forming-cells
#12
Dawei Wang, Yimeng Song, Jianshu Zhang, Wei Pang, Xian Wang, Yi Zhu, Xiaoxia Li
Endothelial colony forming cells (ECFCs) were proved to take part in post-natal vasculogenesis and injury repair. The angiogenic properties of ECFCs could be influenced by various cytokines, chemokines, and growth factors. Erythropoietin (EPO) is a promising cytokine participating in angiogenesis. However, the mechanisms for EPO's proangiogenic effect still remain largely elusive. Here, we investigated the role of AMP-activated protein kinase (AMPK)-Krüppel-like factor 2 (KLF2) signaling pathway in the proangiogenic effect of EPO in ECFCs...
October 4, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28977827/analysis-of-region-specific-gene-expression-patterns-in-the-heart-and-systemic-responses-after-experimental-myocardial-ischemia
#13
Matthias Zimmermann, Lucian Beer, Robert Ullrich, Dominika Lukovic, Elisabeth Simader, Denise Traxler, Tanja Wagner, Lucas Nemec, Lukas Altenburger, Andreas Zuckermann, Mariann Gyöngyösi, Hendrik Jan Ankersmit, Michael Mildner
AIMS: Ischemic myocardial injury leads to the activation of inflammatory mechanisms and results in ventricular remodeling. Although great efforts have been made to unravel the molecular and cellular processes taking place in the ischemic myocardium, little is known about the effects on the surrounding tissue and other organs. The aim of this study was to determine region specific differences in the myocardium and in distant organs after experimental myocardial infarction by using a bioinformatics approach...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977783/kr%C3%A3-ppel-like-factor-7-is-a-marker-of-aggressive-gastric-cancer-and-poor-prognosis
#14
Zhonghua Jiang, Tingting Yu, Zhining Fan, Hongmei Yang, Xin Lin
BACKGROUND/AIMS: Krüppel-like factor (KLF) 7 protein is a member of the KLF transcription factor family, which plays important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation and metabolism. However, the role of KLF7 in gastric cancer (GC) is unknown. The aim of this study is to explore the role of KLF7 in GC and its correlation with clinicopathological characteristics and prognosis of GC patients. METHODS: We first systematically evaluated dysregulation of the KLF family in The Cancer Genome Atlas (TCGA) GC database...
October 5, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28973434/dcas9-based-epigenome-editing-suggests-acquisition-of-histone-methylation-is-not-sufficient-for-target-gene-repression
#15
Henriette O'Geen, Chonghua Ren, Charles M Nicolet, Andrew A Perez, Julian Halmai, Victoria M Le, Joel P Mackay, Peggy J Farnham, David J Segal
Distinct epigenomic profiles of histone marks have been associated with gene expression, but questions regarding the causal relationship remain. Here we investigated the activity of a broad collection of genomically targeted epigenetic regulators that could write epigenetic marks associated with a repressed chromatin state (G9A, SUV39H1, Krüppel-associated box (KRAB), DNMT3A as well as the first targetable versions of Ezh2 and Friend of GATA-1 (FOG1)). dCas9 fusions produced target gene repression over a range of 0- to 10-fold that varied by locus and cell type...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28972010/thyroid-hormone-regulates-hematopoiesis-via-the-tr-klf9-axis
#16
Ying Zhang, Yuanyuan Xue, Chunwei Cao, Jiaojiao Huang, Qianlong Hong, Tang Hai, Qitao Jia, Xianlong Wang, Guosong Qin, Jing Yao, Xiao Wang, Qiantao Zheng, Rui Zhang, Yongshun Li, Ailing Luo, Nan Zhang, Guizhi Shi, Yanfang Wang, Hao Ying, Zhonghua Liu, Hongmei Wang, Anming Meng, Qi Zhou, Hong Wei, Feng Liu, Jianguo Zhao
Congenital hypothyroidism (CH) is one of the most prevalent endocrine diseases and is often accompanied by anemia and immunodeficiency in patients, for which the underlying mechanisms remain unknown. Here we created a severe CH model together with anemia and T lymphopenia to mimic the clinical features of hypothyroid patients by ethylnitrosourea (ENU) mutagenesis in Bama miniature pigs. A novel recessive c.1226A>G transition of the dual oxidase 2 (DUOX2) gene was identified as the causative mutation. This mutation hindered the production of hydrogen peroxide (H2O2) and thus contributed to thyroid hormone (TH) synthesis failure...
September 25, 2017: Blood
https://www.readbyqxmd.com/read/28963353/somatic-super-enhancer-duplications-and-hotspot-mutations-lead-to-oncogenic-activation-of-the-klf5-transcription-factor
#17
Xiaoyang Zhang, Peter S Choi, Joshua M Francis, Galen F Gao, Joshua D Campbell, Aruna Ramachandran, Yoichiro Mitsuishi, Gavin Ha, Juliann Shih, Francisca Vazquez, Aviad Tsherniak, Alison M Taylor, Jin Zhou, Zhong Wu, Ashton C Berger, Marios Giannakis, William C Hahn, Andrew D Cherniack, Matthew Meyerson
The Krüppel-like family of transcription factors (KLF) plays critical roles in human development and is associated with cancer pathogenesis. KLF5 has been shown to promote cancer cell proliferation and tumorigenesis, and to be genomically amplified in cancer cells. We recently reported that the KLF5 gene is also subject to other types of somatic coding and noncoding genomic alterations in diverse cancer types. Here we show that these alterations activate KLF5 by three distinct mechanisms. 1) Focal amplification of super-enhancers activates KLF5 expression in squamous cell carcinomas...
September 29, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28962896/germline-deletion-of-kr%C3%A3-ppel-like-factor-14-does-not-increase-risk-of-diet-induced-metabolic-syndrome-in-male-c57bl-6-mice
#18
Carmen A Argmann, Sara Violante, Tetyana Dodatko, Mariana P Amaro, Jacob Hagen, Virginia L Gillespie, Christoph Buettner, Eric E Schadt, Sander M Houten
OBJECTIVE: The transcription factor Krüppel-like factor 14 (KLF14) has been associated with type 2 diabetes and high-density lipoprotein-cholesterol (HDL-C) through genome-wide association studies. The mechanistic underpinnings of KLF14's control of metabolic processes remain largely unknown. We studied the physiological roles of KLF14 in a knockout (KO) mouse model. METHODS: Male whole body Klf14 KO mice were fed a chow or high fat diet (HFD) and diet induced phenotypes were analyzed...
September 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28953910/potential-mirna-involvement-in-the-anti-adipogenic-effect-of-resveratrol-and-its-metabolites
#19
Itziar Eseberri, Arrate Lasa, Jonatan Miranda, Ana Gracia, Maria P Portillo
OBJECTIVE: Scientific research is constantly striving to find molecules which are effective against excessive body fat and its associated complications. Taking into account the beneficial effects that resveratrol exerts on other pathologies through miRNA, the aim of the present work was to analyze the possible involvement of miRNAs in the regulation of adipogenic transcription factors peroxisome proliferator-activated receptor γ (pparγ), CCAAT enhancer-binding proteins α and β (cebpβ and cebpα) induced by resveratrol and its metabolites...
2017: PloS One
https://www.readbyqxmd.com/read/28943967/kr%C3%A3-ppel-like-factor-8-induces-epithelial-to-mesenchymal-transition-and-promotes-invasion-of-pancreatic-cancer-cells-through-transcriptional-activation-of-four-and-a-half-lim-only-protein-2
#20
Xiaoping Yi, Hongyan Zai, Xueying Long, Xiaoyi Wang, Wenzheng Li, Yixiong Li
Pancreatic cancer (PC) is one of the most aggressive types of cancer with an extremely poor prognosis. Invasive growth and early metastasis is one of the greatest challenges to overcome for the treatment of PC. Numerous previous studies have indicated that the transcription factor Krüppel-like factor 8 (KLF8) and nuclear cofactor four and a half LIM-only protein 2 (FHL2) serve important roles in tumorigenesis and tumor progression; however, their roles in PC remain elusive. The present study revealed that KLF8 and FHL2 expression is aberrantly co-overexpressed in PC tissue samples and associated with tumor metastasis...
October 2017: Oncology Letters
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