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https://www.readbyqxmd.com/read/28507102/foxo3-pgc-1%C3%AE-signaling-axis-is-essential-for-cancer-stem-cell-properties-of-pancreatic-ductal-adenocarcinoma
#1
Motofumi Kumazoe, Mika Takai, Shun Hiroi, Chieri Takeuchi, Mai Kadomatsu, Takashi Nojiri, Hiroaki Onda, Jaehoon Bae, Yuhui Huang, Kanako Takamatsu, Shuya Yamashita, Kenji Kangawa, Hirofumi Tachibana
In 95% of patients with pancreatic ductal adenocarcinoma (PDAC), recurrence is observed following chemotherapy. Findings from several studies have indicated that cancer stem cells (CSCs) are resistant to anti-cancer agents and may be involved in cancer recurrence and metastasis. The CD44 protein is a major CSC marker, and CD44 also plays an indispensable role in the CSC properties in several cancers, including pancreatic cancer; however, no clinical approach exists to inhibit CD44 activity. Here, we have performed knockin/knock down experiments and we demonstrate that the forkhead box O3 (FOXO3)/liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK)/PPAR-γ co-activator-1β (PGC- 1β)/pyruvate dehydrogenase -A1 (PDHA1) pathway is essential for CD44 expression and CSC properties...
May 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28465359/elevated-foxg1-and-sox2-in-glioblastoma-enforces-neural-stem-cell-identity-through-transcriptional-control-of-cell-cycle-and-epigenetic-regulators
#2
Harry Bulstrode, Ewan Johnstone, Maria Angeles Marques-Torrejon, Kirsty M Ferguson, Raul Bardini Bressan, Carla Blin, Vivien Grant, Sabine Gogolok, Ester Gangoso, Sladjana Gagrica, Christine Ender, Vassiliki Fotaki, Duncan Sproul, Paul Bertone, Steven M Pollard
Glioblastoma multiforme (GBM) is an aggressive brain tumor driven by cells with hallmarks of neural stem (NS) cells. GBM stem cells frequently express high levels of the transcription factors FOXG1 and SOX2. Here we show that increased expression of these factors restricts astrocyte differentiation and can trigger dedifferentiation to a proliferative NS cell state. Transcriptional targets include cell cycle and epigenetic regulators (e.g., Foxo3, Plk1, Mycn, Dnmt1, Dnmt3b, and Tet3). Foxo3 is a critical repressed downstream effector that is controlled via a conserved FOXG1/SOX2-bound cis-regulatory element...
May 2, 2017: Genes & Development
https://www.readbyqxmd.com/read/28445867/the-mir-106a-363xpcl1-mirna-cluster-induces-murine-t-cell-lymphoma-despite-transcriptional-activation-of-the-p27kip1-cell-cycle-inhibitor
#3
Daniel A Kuppers, Thomas M Schmitt, Harry C Hwang, Lavanya Samraj, Bruce E Clurman, Matthew L Fero
The miR-106a~363 cluster encodes 6 miRNAs on the X-chromosome which are abundant in blood cells and overexpressed in a variety of malignancies. The constituent miRNA of miR-106a~363 have functional activities in vitro that are predicted to be both oncogenic and tumor suppressive, yet little is known about their physiological functions in vivo. Mature miR-106a~363 (Mirc2) miRNAs are processed from an intragenic, non-protein encoding gene referred to as Xpcl1 (or Kis2), situated at an X-chromosomal locus frequently targeted by retroviruses in murine lymphomas...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444134/characterization-of-foxo1-3-and-4-transcription-factors-in-ovaries-of-fetal-prepubertal-and-adult-rhesus-macaques
#4
Alison Y Ting, Mary B Zelinski
The phosphoinositide 3-kinase/AKT signaling pathway negatively regulates follicle activation via the forkhead box O (FOXO) transcription factor in rodents. FOXO3 knockout mice exhibit global activation of primordial follicles leading to early depletion of ovarian follicles and subsequent infertility. Whether a similar mechanism for follicle activation exists in the primate ovary is unclear. In the current study, protein localization of FOXO1, 3 and 4 as well as their upstream regulator, AKT/p-AKT, were examined in rhesus macaque ovaries of 3 developmental stages: fetal, prepubertal and adult...
April 22, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28436938/geminin-facilitates-foxo3-deacetylation-to-promote-breast-cancer-cell-metastasis
#5
Lei Zhang, Meizhen Cai, Zhicheng Gong, Bingchang Zhang, Yuanpei Li, Li Guan, Xiaonan Hou, Qing Li, Gang Liu, Zengfu Xue, Muh-Hua Yang, Jing Ye, Y Eugene Chin, Han You
Geminin expression is essential for embryonic development and the maintenance of chromosomal integrity. In spite of this protective role, geminin is also frequently overexpressed in human cancers and the molecular mechanisms underlying its role in tumor progression remain unclear. The histone deacetylase HDAC3 modulates transcription factors to activate or suppress transcription. Little is known about how HDAC3 specifies substrates for modulation among highly homologous transcription factor family members. Here, we have demonstrated that geminin selectively couples the transcription factor forkhead box O3 (FoxO3) to HDAC3, thereby specifically facilitating FoxO3 deacetylation...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28432353/severe-hearing-loss-and-outer-hair-cell-death-in-homozygous-foxo3-knockout-mice-after-moderate-noise-exposure
#6
Felicia Gilels, Stephen T Paquette, Holly J Beaulac, Anwen Bullen, Patricia M White
Noise induced hearing loss (NIHL) is a disease that affects millions of Americans. Identifying genetic pathways that influence recovery from noise exposure is an important step forward in understanding NIHL. The transcription factor Foxo3 integrates the cellular response to oxidative stress and plays a role in extending lifespan in many organisms, including humans. Here we show that Foxo3 is required for auditory function after noise exposure in a mouse model system, measured by ABR. Absent Foxo3, outer hair cells are lost throughout the middle and higher frequencies...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28430387/age-related-reduction-in-the-expression-of-foxo-transcription-factors-and-correlations-with-intervertebral-disc-degeneration
#7
Oscar Alvarez-Garcia, Tokio Matsuzaki, Merissa Olmer, Koichi Masuda, Martin K Lotz
Aging is a main risk factor for intervertebral disc (IVD) degeneration, the main cause of low back pain. FOXO transcription factors are important regulators of tissue homeostasis and longevity. Here, we determined the expression pattern of FOXO in healthy and degenerated human IVD and the associations with IVD degeneration during mouse aging. FOXO expression was assessed by immunohistochemistry in normal and degenerated human IVD samples and in cervical and lumbar IVD from 6-, 12-, 24-, and 36-month-old C57BL/6J mice...
April 21, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28415610/the-tubulin-inhibitor-mg-2477-induces-autophagy-regulated-cell-death-ros-accumulation-and-activation-of-foxo3-in-neuroblastoma
#8
Judith Hagenbuchner, Lorena Lungkofler, Ursula Kiechl-Kohlendorfer, Giampietro Viola, Maria Grazia Ferlin, Michael J Ausserlechner, Petra Obexer
Neuroblastoma is the most frequent extra-cranial solid tumor in children with still high mortality in stage M. Here we studied the tubulin-inhibitor MG-2477 as a possible therapeutic agent for neuroblastoma therapy and uncovered that MG-2477 induces death in neuroblastoma cells independent of PKB-activation status and stage. MG-2477 triggers within 30 minutes extensive autophagosome-formation that finally leads to cell death associated with mitotic catastrophe. Autophagy is critical for MG-2477-induced death and is regulated by the BH3-only protein PMAIP1/NOXA which sequesters the anti-apoptotic BCL2-protein BCLXL and thereby displaces and activates the autophagy-regulator BECN1/beclin1...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411009/skeletal-muscle-morphology-and-regulatory-signalling-in-endurance-trained-and-sedentary-individuals-the-influence-of-ageing
#9
U R Mikkelsen, J Agergaard, C Couppé, J F Grosset, A Karlsen, S P Magnusson, P Schjerling, M Kjaer, A L Mackey
Muscle mass in humans is inversely associated with circulating levels of inflammatory cytokines, but the interaction between ageing and training on muscle composition and the intra-muscular signalling behind inflammation and contractile protein synthesis and degradation is unknown. We studied 15 healthy life-long endurance runners, 12 age-matched untrained controls, 10 young trained and 12 young untrained individuals. Thigh muscle composition was investigated by magnetic resonance imaging (MRI), where non-contractile intramuscular tissue (NCIT) area (fat and connective tissue) was found to be greater in older but lower in trained individuals...
July 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28401267/paeonol-protects-against-tnf-%C3%AE-induced-proliferation-and-cytokine-release-of-rheumatoid-arthritis-fibroblast-like-synoviocytes-by-upregulating-foxo3-through-inhibition-of-mir-155-expression
#10
Ning Liu, Xue Feng, Wenbo Wang, Xingkai Zhao, Xia Li
BACKGROUND: Fibroblast-like synoviocytes (FLS) play an essential role in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis. Paeonol (Pae) is a phenolic compound found in many traditional Chinese medicine remedies. However, the effects of Pae on TNF-α-stimulated FLS and the underlying molecular mechanism are unknown. In this study, we aimed to investigate the anti-proliferative and anti-inflammatory effect of Pae against activated FLS. MATERIALS AND METHODS: Rheumatoid arthritis FLS (RA-FLS) were pre-treated with different doses (25, 50, and 100 µM) of Pae or miR-155 inhibitor for 30 min or transfected with miR-155 mimic, and then treated with 50 ng/mL of tumor necrosis factor alpha (TNF-α) for 1 h...
April 11, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28398822/a-peroxidase-peroxiredoxin-1-specific-redox-regulation-of-the-novel-foxo3-microrna-target-let-7
#11
Barbara L Hopkins, Monica Nadler, John J Skoko, Thierry Bertomeu, Andrea Pelosi, Parisa Mousavi Shafaei, Kevin Levine, Anja Schempf, Bodvael Pennarun, Bo Yang, Dipak Datta, Steffi Oesterreich, Da Yang, Maria Rozzi, Roya Khosravi-Far, Carola A Neumann
Precision in redox signaling is attained through posttranslational protein modifications such as oxidation of protein thiols. The peroxidase peroxiredoxin 1 (PRDX1) regulates signal transduction through changes in thiol oxidation of its cysteines. We demonstrate here that PRDX1 is a binding partner for the tumor suppressive transcription factor FOXO3 that directly regulates the FOXO3 stress response. Heightened oxidative stress evokes formation of disulfide-bound heterotrimers linking dimeric PRDX1 to monomeric FOXO3...
May 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28388574/over-expression-of-growth-differentiation-factor-15-gdf15-preventing-cold-ischemia-reperfusion-i-r-injury-in-heart-transplantation-through-foxo3a-signaling
#12
Yixin Zhang, Lisa A Moszczynski, Qing Liu, Jifu Jiang, Duo Zhao, Douglas Quan, Tina Mele, Vivian McAlister, Anthony Jevnikar, Seung Joon Baek, Kexiang Liu, Xiufen Zheng
Ischemia reperfusion (I/R) injury which inevitably occurs during heart transplantation is the major factor leading to organ failure and graft rejection. In order to develop new therapies to prevent I/R injury, we used both a murine heart transplantation model with 24 hour cold I/R and an in vitro cell culture system to determine whether growth differentiation factor 15 (GDF15) is a protective factor in preventing I/R injury in heart transplantation and to further investigate underlying mechanisms of I/R injury...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28379301/embryo-arrest-and-reactivation-potential-candidates-controlling-embryonic-diapause-in-the-tammar-wallaby-and-mink%C3%A2
#13
Jane C Fenelon, Geoffrey Shaw, Stephen R Frankenberg, Bruce D Murphy, Marilyn B Renfree
Embryonic diapause is a period of developmental arrest which requires coordination of a molecular cross-talk between the endometrium and blastocyst to ensure a successful reactivation, but the exact mechanisms are undefined. The objectives of this study were to screen the tammar blastocyst for potential diapause control factors and to investigate the potential for members of the epidermal growth factor (EGF) family to coordinate reactivation. A select number of factors were also examined in the mink to determine whether their expression patterns were conserved across diapause species...
April 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28356085/cnv-discovery-for-milk-composition-traits-in-dairy-cattle-using-whole-genome-resequencing
#14
Yahui Gao, Jianping Jiang, Shaohua Yang, Yali Hou, George E Liu, Shengli Zhang, Qin Zhang, Dongxiao Sun
BACKGROUND: Copy number variations (CNVs) are important and widely distributed in the genome. CNV detection opens a new avenue for exploring genes associated with complex traits in humans, animals and plants. Herein, we present a genome-wide assessment of CNVs that are potentially associated with milk composition traits in dairy cattle. RESULTS: In this study, CNVs were detected based on whole genome re-sequencing data of eight Holstein bulls from four half- and/or full-sib families, with extremely high and low estimated breeding values (EBVs) of milk protein percentage and fat percentage...
March 29, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28349111/dataset-of-the-human-homologues-and-orthologues-of-lipid-metabolic-genes-identified-as-daf-16-targets-their-roles-in-lipid-and-energy-metabolism
#15
Lavender Yuen-Nam Fan, Paula Saavedra-García, Eric Wing-Fai Lam
The data presented in this article are related to the review article entitled 'Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis' (Saavedra-Garcia et al., 2017) [24]. Here, we have matched the DAF-16/FOXO3 downstream genes with their respective human orthologues and reviewed the roles of these targeted genes in FA metabolism. The list of genes listed in this article are precisely selected from literature reviews based on their functions in mammalian FA metabolism. The nematode Caenorhabditis elegans gene orthologues of the genes are obtained from WormBase, the online biological database of C...
April 2017: Data in Brief
https://www.readbyqxmd.com/read/28341621/cancer-cachexia-induced-muscle-atrophy-evidence-for-alterations-in-micrornas-important-for-muscle-size
#16
David Edward Lee, Jacob L Brown, Megan E Rosa-Caldwell, Thomas A Blackwell, Richard A Perry, Lemuel A Brown, Bhuwan Khatri, Dongwon Seo, Walter Gay Bottje, Tyrone Anthony Washington, Michael P Wiggs, Byung-Whi Kong, Nicholas Perry Greene
Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20-40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy, however less is known specifically on miRNAs in cancer cachexia. PURPOSE: The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition...
March 24, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28330873/amp-activated-protein-kinase-%C3%AE-1-promotes-atherogenesis-by-increasing-monocyte-to-macrophage-differentiation
#17
Miao Zhang, Huaiping Zhu, Ye Ding, Zhaoyu Liu, Zhejun Cai, Ming-Hui Zou
Monocyte-to-macrophage differentiation, which can be initiated by physiological or atherogenic factors, is a pivotal process in atherogenesis, a disorder in which monocytes adhere to endothelial cells and subsequently migrate into the subendothelial spaces, where they differentiate into macrophages and macrophage-derived foam cells and cause atherosclerotic lesions. However, the monocyte-differentiation signaling pathways that are activated by atherogenic factors are poorly defined. Here we report that the AMP-activated protein kinase α1 (AMPKα1) in monocytes promotes atherosclerosis by increasing monocyte differentiation and survival...
May 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28321785/microrna-34a-suppresses-autophagy-in-alveolar-type-ii-epithelial-cells-in-acute-lung-injury-by-inhibiting-foxo3-expression
#18
Lan Song, Fangliang Zhou, Lijuan Cheng, Mei Hu, Yingchun He, Bo Zhang, Duanfang Liao, Zhaojun Xu
Excessive autophagic activity of alveolar type II epithelial (AT-II) cells is one of the main causes of acute lung injury (ALI); however, the underlying molecular mechanism remains to be determined. The microRNAs (miRNAs) are involved with autophagy in many diseases. The objective of this study was therefore to investigate the relationship between the miRNA expression and the autophagic activity of the AT-II cells in the pathogenesis of ALI and its molecular mechanism. A mouse model of ALI and AT-II cell injury was induced using lipopolysaccharide (LPS) in vivo and in vitro, and the expression of miR-34a and the autophagy-related proteins LC3 II/I and p62 were determined...
March 21, 2017: Inflammation
https://www.readbyqxmd.com/read/28315775/assessment-of-histone-tail-modifications-and-transcriptional-profiling-during-colon-cancer-progression-reveals-a-global-decrease-in-h3k4me3-activity
#19
Karen Triff, Mathew W McLean, Kranti Konganti, Jiahui Pang, Evelyn Callaway, Beiyan Zhou, Ivan Ivanov, Robert S Chapkin
During colon cancer, epigenetic alterations contribute to the dysregulation of major cellular functions and signaling pathways. Modifications in chromatin signatures such as H3K4me3 and H3K9ac, which are associated with transcriptionally active genes, can lead to genomic instability and perturb the expression of gene sets associated with oncogenic processes. In order to further elucidate early pre-tumorigenic epigenetic molecular events driving CRC, we integrated diverse, genome-wide, epigenetic inputs (by high throughput sequencing of RNA, H3K4me3, and H3K9ac) and compared differentially expressed transcripts (DE) and enriched regions (DER) in an in-vivo rat colon cancer progression model...
March 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315332/nuclear-ampk-regulated-carm1-stabilization-impacts-autophagy-in-aged-heart
#20
Chen Li, Lu Yu, Han Xue, Zheng Yang, Yue Yin, Bo Zhang, Mai Chen, Heng Ma
Senescence-associated autophagy downregulation leads to cardiomyocyte dysfunction. Coactivator-associated arginine methyltransferase 1 (CARM1) participates in many cellular processes, including autophagy in mammals. However, the effect of CARM1 in aging-related cardiac autophagy decline remains undefined. Moreover, AMP-activated protein kinase (AMPK) is a key regulator in metabolism and autophagy, however, the role of nuclear AMPK in autophagy outcome in aged hearts still unclear. Hers we identify the correlation between nuclear AMPK and CARM1 in aging heart...
April 29, 2017: Biochemical and Biophysical Research Communications
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