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https://www.readbyqxmd.com/read/29335523/mir-139-5p-inhibits-aerobic-glycolysis-cell-proliferation-migration-and-invasion-in-hepatocellular-carcinoma-via-a-reciprocal-regulatory-interaction-with-ets1
#1
Shengni Hua, Ling Lei, Ling Deng, Xie Weng, Chengdong Liu, Xiaolong Qi, Shuang Wang, Dongyan Zhang, Xuejing Zou, Chuanhui Cao, Li Liu, Dehua Wu
Cancer cells have metabolic features that allow them to preferentially metabolize glucose through aerobic glycolysis, providing them with a progression advantage. However, microRNA (miRNA) regulation of aerobic glycolysis in cancer cells has not been extensively investigated. We addressed this in the present study by examining the regulation of miR-139-5p on aerobic glycolysis of hepatocellular carcinoma (HCC) using clinical specimens, HCC cells, and a mouse xenograft model. We found that overexpressing miR-139-5p restrained aerobic glycolysis, suppressing proliferation, migration, and invasion in HCC cells...
January 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29335521/non-canonical-roles-of-pfkfb3-in-regulation-of-cell-cycle-through-binding-to-cdk4
#2
Wenzhi Jia, Xiaoping Zhao, Li Zhao, Hui Yan, Jiajin Li, Hao Yang, Gang Huang, Jianjun Liu
There is growing interest in studying the molecular mechanisms of crosstalk between cancer metabolism and the cell cycle. 6-phosphate fructose-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) is a well-known glycolytic activator that plays an important role in tumorigenesis. We investigated whether PFKFB3 was directly involved in oncogenic signaling networks. Mass Spectrometry showed that PFKFB3 interacts with cyclin-dependent kinase (CDK) 4, which controls the transition from G1 phase to S phase of the cell cycle...
January 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29327288/expression-of-pfkfb3-and-ki67-in-lung-adenocarcinomas-and-targeting-pfkfb3-as-a-therapeutic-strategy
#3
Xiaoli Li, Jian Liu, Li Qian, Honggang Ke, Chan Yao, Wei Tian, Yifei Liu, Jianguo Zhang
Phosphofructokinase-2/fructose-2, 6-bisphosphatase 3 (PFKFB3) catalyzes the synthesis of F2,6BP, which is an allosteric activator of 6-phosphofructo-1-kinase (PFK-1): the rate-limiting enzyme of glycolysis. During tumorigenesis, PFKFB3 increases glycolysis, angiogenesis, and tumor progression. In this study, our aim was to investigate the significance of PFKFB3 and Ki67 in human lung adenocarcinomas and to target PFKFB3 as a therapeutic strategy. In this study, we determined the expression levels of PFKFB3 mRNA and proteins in cancerous and normal lung adenocarcinomas by quantitative reverse transcription PCR (qRT-PCR), Western blot analysis, and tissue microarray immunohistochemistry analysis, respectively...
January 11, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29275212/nrf2-facilitates-breast-cancer-cell-growth-via-hif1%C3%A9-mediated-metabolic-reprogramming
#4
Hong-Sheng Zhang, Guang-Yuan Du, Zhong-Guo Zhang, Zhen Zhou, Hong-Liang Sun, Xiao-Ying Yu, Yu-Ting Shi, Dan-Ning Xiong, Hu Li, Ying-Hui Huang
High aerobic glycolysis not only provides energy to breast cancer cells, but also supports their anabolic growth. The redox sensitive transcription factor NRF2 is over-expressed in multiple cancers, including breast cancer. It is unclear whether NRF2 could promote breast cancer cell growth through enhancing glycolysis. In this study, we found that NRF2 and HIF1α mRNA and protein levels were significantly increased in MCF-7 and MDA-MB-231 breast cancer cells as compared to MCF-10A benign breast epithelial cells...
December 21, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29162555/11%C3%AE-hydroxysteroid-dehydrogenase-1-deficiency-alters-brain-energy-metabolism-in-acute-systemic-inflammation
#5
Manu Verma, Tiina M J Kipari, Zhenguang Zhang, Tak Yung Man, Thorsten Forster, Natalie Z M Homer, Jonathan R Seckl, Megan C Holmes, Karen E Chapman
Chronically elevated glucocorticoid levels impair cognition and are pro-inflammatory in the brain. Deficiency or inhibition of 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), which converts inactive into active glucocorticoids, protects against glucocorticoid-associated chronic stress- or age-related cognitive impairment. Here, we hypothesised that 11β-HSD1 deficiency attenuates the brain cytokine response to inflammation. Because inflammation is associated with altered energy metabolism, we also examined the effects of 11β-HSD1 deficiency upon hippocampal energy metabolism...
November 21, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29161413/nrf2-regulates-endothelial-glycolysis-and-proliferation-with-mir-93-and-mediates-the-effects-of-oxidized-phospholipids-on-endothelial-activation
#6
Suvi M Kuosmanen, Emilia Kansanen, Minna U Kaikkonen, Virve Sihvola, Kati Pulkkinen, Henna-Kaisa Jyrkkänen, Pauli Tuoresmäki, Juha Hartikainen, Mikko Hippeläinen, Hannu Kokki, Pasi Tavi, Sami Heikkinen, Anna-Liisa Levonen
Phospholipids, such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC), are the major components of cell membranes. Their exposure to reactive oxygen species creates oxidized phospholipids, which predispose to the development of chronic inflammatory diseases and metabolic disorders through endothelial activation and dysfunction. Although the effects of oxidized PAPC (oxPAPC) on endothelial cells have been previously studied, the underlying molecular mechanisms evoking biological responses remain largely unknown...
November 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29151977/pfkfb3-promotes-proliferation-migration-and-angiogenesis-in-nasopharyngeal-carcinoma
#7
Miao Gu, Li Li, Zhenxin Zhang, Jing Chen, Wei Zhang, Jie Zhang, Liang Han, Mingming Tang, Bo You, Qicheng Zhang, Yiwen You
Nasopharyngeal carcinoma (NPC) is a squamous epithelial cancer, arising from the nasopharynx epithelium. It has high morbidity and mortality. PFKFB3 as a glycolytic activator has been implicated in the progression of multiple types of tumor. PFKFB3 can be contributed to the progression and metastasis of cancer. However, whether PFKFB3 is associated with the progression of NPC remains unknown. We postulated that PFKFB3 promotes proliferation, migration and angiogenesis in nasopharyngeal carcinoma. In this study, we found that PFKFB3 was significantly up-regulated in NPC tissues and cell lines compared with normal control...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29113354/6-phosphofructo-2-kinase-fructose-2-6-bisphosphatase-isoform-3-spatially-mediates-autophagy-through-the-ampk-signaling-pathway
#8
Siyuan Yan, Xiaoli Wei, Shanshan Xu, Hui Sun, Weijun Wang, Ling Liu, Xuejun Jiang, Yongxiang Zhang, Yongsheng Che
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3), is a critical enzyme for glycolysis and highly expressed in cancer cells. It plays an essential role in regulating metabolism, angiogenesis, and inflammation. Although PFKFB3 is involved in modulating autophagy, its regulatory role appears to be either positive or negative, which remains to be clarified. Unlike other PFK-2/FBPase isoforms, PFKFB3 can localize in both nucleus and cytoplasm, leading to the speculation that subcellular localization of PFKFB3 may play a regulatory role in autophagy...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29101015/dna-damage-metabolism-and-aging-in-pro-inflammatory-t-cells-rheumatoid-arthritis-as-a-model-system
#9
REVIEW
Yinyin Li, Jörg J Goronzy, Cornelia M Weyand
The aging process is the major driver of morbidity and mortality, steeply increasing the risk to succumb to cancer, cardiovascular disease, infection and neurodegeneration. Inflammation is a common denominator in age-related pathologies, identifying the immune system as a gatekeeper in aging overall. Among immune cells, T cells are long-lived and exposed to intense replication pressure, making them sensitive to aging-related abnormalities. In successful T cell aging, numbers of naïve cells, repertoire diversity and activation thresholds are preserved as long as possible; in maladaptive T cell aging, protective T cell functions decline and pro-inflammatory effector cells are enriched...
November 8, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29072034/potential-effect-of-exercise-in-ameliorating-insulin-resistance-at-transcriptome-level
#10
Zhigang Hu, Lei Zhou, Tingting He
BACKGROUND: Insulin resistance can lead to the pathogenesis of type 2 diabetes and exercise can increase insulin sensitivity. And different exercises may have different influences on the mitigation of insulin resistance. It's still unclear how exercise affects inherited insulin resistance at transcriptome level. The purpose of our study was to analyze the potential effects of exercise in ameliorating insulin resistance at transcriptome level. METHODS: Herein, we analyzed two skeletal muscle transcriptome profiles, including gene profiles between inherited insulin resistant patients and matched healthy controls, and between trained and sedentary subjects (young and old subjects, respectively)...
October 24, 2017: Journal of Sports Medicine and Physical Fitness
https://www.readbyqxmd.com/read/29061364/inflammatory-microglia-are-glycolytic-and-iron-retentive-and-typify-the-microglia-in-app-ps1-mice
#11
R Holland, A L McIntosh, O M Finucane, V Mela, A Rubio-Araiz, G Timmons, S A McCarthy, Y K Gun'ko, M A Lynch
Microglia, like macrophages, can adopt inflammatory and anti-inflammatory phenotypes depending on the stimulus. In macrophages, the evidence indicates that these phenotypes have different metabolic profiles with lipopolysaccharide (LPS)- or interferon-γ (IFNγ)-stimulated inflammatory cells switching to glycolysis as their main source of ATP and interleukin-4 (IL-4)-stimulated cells utilizing oxidative phosphorylation. There is a paucity of information regarding the metabolic signatures of inflammatory and anti-inflammatory microglia...
October 20, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28977989/the-molecular-basis-of-targeting-pfkfb3-as-a-therapeutic-strategy-against-cancer
#12
Luo Lu, Yaoyu Chen, Yu Zhu
6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatases (PFKFBs) are bifunctional enzymes which regulate the transformation between fructose-2, 6-bisphosphate (F2, 6BP) and fructose-6-phosphate (F6P) in the process of glucose metabolism. Among the four isozymes (PFKFB1-4), PFKFB3 has stronger kinase activity than phosphatase activity, resulting in the synthesis of F2, 6BP and the promotion of glycolysis. Additionally, PFKFB3 plays a key role in cell cycle regulation. It has been confirmed that PFKFB3 is upregulated in a variety of tumor cells, and inhibition of it results in suppression of the growth of tumor cells by downregulating the glycolytic flux...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28963395/lncrna-wires-up-hippo-and-hedgehog-signaling-to-reprogramme-glucose-metabolism
#13
Xin Zheng, Han Han, Guang-Ping Liu, Yan-Xiu Ma, Ruo-Lang Pan, Ling-Jie Sang, Rui-Hua Li, Luo-Jia Yang, Jeffrey R Marks, Wenqi Wang, Aifu Lin
The Hippo pathway plays essential roles in organ size control and cancer prevention via restricting its downstream effector, Yes-associated protein (YAP). Previous studies have revealed an oncogenic function of YAP in reprogramming glucose metabolism, while the underlying mechanism remains to be fully clarified. Accumulating evidence suggests long noncoding RNAs (lncRNAs) as attractive therapeutic targets, given their roles in modulating various cancer-related signaling pathways. In this study, we report that lncRNA breast cancer anti-estrogen resistance 4 (BCAR4) is required for YAP-dependent glycolysis...
November 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28945981/a-high-throughput-screening-triage-workflow-to-authenticate-a-novel-series-of-pfkfb3-inhibitors
#14
Stephen A St-Gallay, Neil Bennett, Susan E Critchlow, Nicola Curtis, Gareth Davies, Judit Debreczeni, Nicola Evans, Ian Hardern, Geoff Holdgate, Neil P Jones, Lindsey Leach, Sarita Maman, Sheila McLoughlin, Marian Preston, Laurent Rigoreau, Andrew Thomas, Andrew P Turnbull, Graeme Walker, Jarrod Walsh, Richard A Ward, Ed Wheatley, Jon Winter-Holt
A high-throughput screen (HTS) of human 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) resulted in several series of compounds with the potential for further optimization. Informatics was used to identify active chemotypes with lead-like profiles and remove compounds that commonly occurred as actives in other HTS screens. The activities were confirmed with IC50 measurements from two orthogonal assay technologies, and further analysis of the Hill slopes and comparison of the ratio of IC50 values at 10 times the enzyme concentration were used to identify artifact compounds...
September 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28935506/endothelial-specific-sirt3-deletion-impairs-glycolysis-and-angiogenesis-and-causes-diastolic-dysfunction
#15
Xiaochen He, Heng Zeng, Sean T Chen, Richard J Roman, Judy L Aschner, Sean Didion, Jian-Xiong Chen
Endothelial glycolysis plays a critical role in the regulation of angiogenesis. We investigated the role of Sirtuin 3 (SIRT3) on endothelial cell (EC) glycolytic metabolism, angiogenesis, and diastolic function. Our aim was to test the hypothesis that loss of SIRT3 in ECs impairs endothelial glycolytic metabolism and angiogenesis and contributes to myocardial capillary rarefaction and the development of diastolic dysfunction. Using SIRT3 deficient ECs, SIRT3 was found to regulate a metabolic switch between mitochondrial respiration and glycolysis...
November 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28875379/tumor-vessel-disintegration-by-maximum-tolerable-pfkfb3-blockade
#16
Lena-Christin Conradi, Aleksandra Brajic, Anna Rita Cantelmo, Ann Bouché, Joanna Kalucka, Andreas Pircher, Ulrike Brüning, Laure-Anne Teuwen, Stefan Vinckier, Bart Ghesquière, Mieke Dewerchin, Peter Carmeliet
Blockade of the glycolytic activator PFKFB3 in cancer cells (using a maximum tolerable dose of 70 mg/kg of the PFKFB3 blocker 3PO) inhibits tumor growth in preclinical models and is currently being tested as a novel anticancer treatment in phase I clinical trials. However, a detailed preclinical analysis of the effects of such maximum tolerable dose of a PFKFB3 blocker on the tumor vasculature is lacking, even though tumor endothelial cells are hyper-glycolytic. We report here that a high dose of 3PO (70 mg/kg), which inhibits cancer cell proliferation and reduces primary tumor growth, causes tumor vessel disintegration, suppresses endothelial cell growth for protracted periods, (model-dependently) aggravates tumor hypoxia, and compromises vascular barrier integrity, thereby rendering tumor vessels more leaky and facilitating cancer cell intravasation and dissemination...
November 2017: Angiogenesis
https://www.readbyqxmd.com/read/28875330/liposomes-co-loaded-with-6-phosphofructo-2-kinase-fructose-2-6-biphosphatase-3-pfkfb3-shrna-plasmid-and-docetaxel-for-the-treatment-of-non-small-cell-lung-cancer
#17
Nusrat Chowdhury, Imran Vhora, Ketan Patel, Ravi Doddapaneni, Arindam Mondal, Mandip Singh
PURPOSE: Non-small cell lung cancer is the leading cause of cancer related deaths globally. Considering the side effects and diminishing chemosensitivity to chemotherapy, novel treatment approaches are sought. Hence, we aim to develop a liposomal co-delivery system of pDNA expressing shRNA against PFKFB3 (pshPFKFB3) and docetaxel (DTX). METHODS: Cationic DTX liposomes complexed with pshPFKFB3 (PSH-DL) were developed. In vitro cell line studies were performed to evaluate transfection, PFKFB3 mRNA silencing, cytotoxicity, pGP inhibition, and protein markers expression...
November 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28857200/by-inhibiting-pfkfb3-aspirin-overcomes-sorafenib-resistance-in-hepatocellular-carcinoma
#18
Sainan Li, Weiqi Dai, Wenhui Mo, Jingjing Li, Jiao Feng, Liwei Wu, Tong Liu, Qiang Yu, Shizan Xu, Wenwen Wang, Xiya Lu, Qinghui Zhang, Kan Chen, Yujing Xia, Jie Lu, Yingqun Zhou, Xiaoming Fan, Ling Xu, Chuanyong Guo
Hepatocellular carcinoma (HCC) is one of the few cancers with a continuous increase in incidence and mortality. Drug resistance is a major problem in the treatment of HCC. In this study, two sorafenib-resistant HCC cell lines and a nude mouse subcutaneously tumor model were used to explore the possible mechanisms leading to sorafenib resistance, and to investigate whether aspirin could increase the sensitivity of hepatoma cells to sorafenib. The combination of aspirin and sorafenib resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo...
December 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28834297/tgf-%C3%AE-1-targets-smad-p38-mapk-and-pi3k-akt-signaling-pathways-to-induce-pfkfb3-gene-expression-and-glycolysis-in-glioblastoma-cells
#19
Ana Rodríguez-García, Paula Samsó, Pere Fontova, Helga Simon-Molas, Anna Manzano, Esther Castaño, Jose Luis Rosa, Ubaldo Martinez-Outshoorn, Francesc Ventura, Àurea Navarro-Sabaté, Ramon Bartrons
In human cancers, transforming growth factor-β1 (TGF-β1) plays a dual role by acting as both a tumor suppressor and a promoter of tumor metastasis. Although TGF-β1 contributes to the metabolic reprogramming of cancer cells and tumor-associated stromal cells, little is known of the molecular mechanisms connecting this cytokine with enhanced glycolysis. PFKFB3 is a homodymeric bifunctional enzyme, belonging to the family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases, that controls the conversion of fructose-6-phosphate (Fru-6-P) to fructose-2,6-bisphosphate (Fru-2,6-P2 )...
October 2017: FEBS Journal
https://www.readbyqxmd.com/read/28765514/the-molecular-basis-of-targeting-pfkfb3-as-a-therapeutic-strategy-against-cancer
#20
REVIEW
Luo Lu, Yaoyu Chen, Yu Zhu
6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatases (PFKFBs) are bifunctional enzymes which regulate the transformation between fructose-2, 6-bisphosphate (F2, 6BP) and fructose-6-phosphate (F6P) in the process of glucose metabolism. Among the four isozymes (PFKFB1-4), PFKFB3 has stronger kinase activity than phosphatase activity, resulting in the synthesis of F2, 6BP and the promotion of glycolysis. Additionally, PFKFB3 plays a key role in cell cycle regulation. It has been confirmed that PFKFB3 is upregulated in a variety of tumor cells, and inhibition of it results in suppression of the growth of tumor cells by downregulating the glycolytic flux...
July 24, 2017: Oncotarget
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