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https://www.readbyqxmd.com/read/29779471/hypoxia-induces-hypoxia-inducible-factor-1%C3%AE-and-potential-hif-responsive-gene-expression-in-uterine-leiomyoma
#1
Hiroshi Ishikawa, Linlin Xu, Kunizui Sone, Tatsuya Kobayashi, Guiwen Wang, Makio Shozu
Uterine leiomyoma is characterized by abundant extracellular matrix and broad avascular areas, both constantly resulting in hypoxia, suggesting some hypoxia-induced response function. Here, we examined whether hypoxia-inducible factor 1α (HIF-1α)- mediated hypoxic response function in uterine leiomyoma. Immunoblotting detected higher basal HIF-1α protein expression in nuclear extracts from uterine leiomyoma tissues than in those from the adjacent myometrium ( P = .0011). Immunohistochemical analysis revealed the presence of HIF-1α-positive cellular components in both leiomyoma and surrounding myometrial tissues...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29620138/pfk15-a-pfkfb3-antagonist-inhibits-autophagy-and-proliferation-in-rhabdomyosarcoma-cells
#2
Chunhui Wang, Jianghong Qu, Siyuan Yan, Quan Gao, Sibin Hao, Dongsheng Zhou
Due to the high-level of metastatic and relapsed rates, rhabdomyosarcoma (RD) patients have a poor prognosis, and novel treatment strategies are required. Thereby, the present study evaluated the efficacy of PFK15, a PFKFB3 inhibitor, in RD cells to explore its potential underlying mechanism on the regulation of autophagy and proliferation in these cells. The effects of PFK15 on cell viability loss and cell death in different treatment groups, were evaluated by MTS assay, colony growth assay and immunoblotting, respectively...
March 29, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29559632/pfkfb3-blockade-inhibits-hepatocellular-carcinoma-growth-by-impairing-dna-repair-through-akt
#3
Wen-Kai Shi, Xiao-Dong Zhu, Cheng-Hao Wang, Yuan-Yuan Zhang, Hao Cai, Xiao-Long Li, Man-Qing Cao, Shi-Zhe Zhang, Kang-Shuai Li, Hui-Chuan Sun
Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key molecule of glucose metabolism in cytoplasm, has been found in various tumors. Emerging evidence has suggested that PFKFB3 is also located in the nucleus and apparent in regulatory functions other than glycolysis. In this study, we found that PFKFB3 expression is associated with hepatocellular carcinoma (HCC) growth and located mainly in the nucleus of tumor cells. PFKFB3 overexpression was associated with large tumor size (p = 0...
March 20, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29511345/targeting-pfkfb3-sensitizes-chronic-myelogenous-leukemia-cells-to-tyrosine-kinase-inhibitor
#4
Yu Zhu, Luo Lu, Chun Qiao, Yi Shan, Huapeng Li, Sixuan Qian, Ming Hong, Huihui Zhao, Jianyong Li, Zhongfa Yang, Yaoyu Chen
Resistance to the BCR-ABL tyrosine kinase inhibitor (TKI) remains a challenge for curing the disease in chronic myeloid leukemia (CML) patients as leukemia cells may survive through BCR-ABL kinase activity-independent signal pathways. To gain insight into BCR-ABL kinase activity-independent mechanisms, we performed an initial bioinformatics screen and followed by a quantitative PCR screen of genes that were elevated in CML samples. A total of 33 candidate genes were identified to be highly expressed in TKIs resistant patients...
March 7, 2018: Oncogene
https://www.readbyqxmd.com/read/29435871/pi3k-akt-signaling-controls-pfkfb3-expression-during-human-t-lymphocyte-activation
#5
Helga Simon-Molas, Claudia Arnedo-Pac, Pere Fontova, Anna Vidal-Alabró, Esther Castaño, Ana Rodríguez-García, Àurea Navarro-Sabaté, Núria Lloberas, Anna Manzano, Ramon Bartrons
Lymphocyte activation is associated with rapid increase of both the glycolytic activator fructose 2,6-bisphosphate (Fru-2,6-P2 ) and the enzyme responsible for its synthesis, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2). PFKFB3 gene, which encodes for the most abundant PFK-2 isoenzyme in proliferating tissues, has been found overexpressed during cell activation in several models, including immune cells. However, there is limited knowledge on the pathways underlying PFKFB3 regulation in human T-lymphocytes, and the role of this gene in human immune response...
February 12, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29410405/acetylation-accumulates-pfkfb3-in-cytoplasm-to-promote-glycolysis-and-protects-cells-from-cisplatin-induced-apoptosis
#6
Fu-Long Li, Jin-Ping Liu, Ruo-Xuan Bao, GuoQuan Yan, Xu Feng, Yan-Ping Xu, Yi-Ping Sun, Weili Yan, Zhi-Qiang Ling, Yue Xiong, Kun-Liang Guan, Hai-Xin Yuan
Enhanced glycolysis in cancer cells has been linked to cell protection from DNA damaging signals, although the mechanism is largely unknown. The 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) catalyzes the generation of fructose-2,6-bisphosphate, a potent allosteric stimulator of glycolysis. Intriguingly, among the four members of PFKFB family, PFKFB3 is uniquely localized in the nucleus, although the reason remains unclear. Here we show that chemotherapeutic agent cisplatin promotes glycolysis, which is suppressed by PFKFB3 deletion...
February 6, 2018: Nature Communications
https://www.readbyqxmd.com/read/29399631/dna-methylation-as-a-mediator-of-the-association-between-prenatal-adversity-and-risk-factors-for-metabolic-disease-in-adulthood
#7
Elmar W Tobi, Roderick C Slieker, René Luijk, Koen F Dekkers, Aryeh D Stein, Kate M Xu, P Eline Slagboom, Erik W van Zwet, L H Lumey, Bastiaan T Heijmans
Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342,596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formal mediation analysis...
January 2018: Science Advances
https://www.readbyqxmd.com/read/29393396/pfkfb3-is-involved-in-breast-cancer-proliferation-migration-invasion-and-angiogenesis
#8
Fang Peng, Qiang Li, Jia-Yuan Sun, Ying Luo, Ming Chen, Yong Bao
6-Phosphofructo 2-kinase/fructose 2, 6-bisphosphatase 3 (PFKFB3) has been reported to be overexpressed in human cancer tissues and to promote the proliferation and migration of cancer cells. However, the role of PFKFB3 in the progression and prognosis of breast cancer is not yet fully understood. In the present study, we investigated the specific role of PFKFB3 in breast cancer progression and its preliminary mechanisms of action. We first used an immunohistochemistry assay to determine that PFKFB3 was highly expressed in breast cancer tissues and that this high level of expression was involved in the poor overall survival of patients with breast cancer...
March 2018: International Journal of Oncology
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
#9
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...
March 2018: Oncogene
https://www.readbyqxmd.com/read/29335521/non-canonical-roles-of-pfkfb3-in-regulation-of-cell-cycle-through-binding-to-cdk4
#10
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...
March 2018: Oncogene
https://www.readbyqxmd.com/read/29327288/expression-of-pfkfb3-and-ki67-in-lung-adenocarcinomas-and-targeting-pfkfb3-as-a-therapeutic-strategy
#11
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
#12
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...
February 2018: 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
#13
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...
March 2018: 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
#14
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...
February 16, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29151977/pfkfb3-promotes-proliferation-migration-and-angiogenesis-in-nasopharyngeal-carcinoma
#15
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
#16
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
#17
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...
May 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29072034/potential-effect-of-exercise-in-ameliorating-insulin-resistance-at-transcriptome-level
#18
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
#19
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...
February 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28977989/the-molecular-basis-of-targeting-pfkfb3-as-a-therapeutic-strategy-against-cancer
#20
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
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