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https://www.readbyqxmd.com/read/28522551/inhibition-of-mir-143-during-ischemia-cerebral-injury-protects-neurons-through-recovery-of-the-hexokinase-2-mediated-glucose%C3%A2-uptake
#1
Xianzhu Zeng, Na Liu, Jing Zhang, Lei Wang, Zhecheng Zhang, Ju Zhu, Qian Li, Yuwen Wang
Ischemic stroke, a major cause of death, is caused by occlusion of a blood vessel, resulting in a significant reduction in regional cerebral blood flow. MicroRNAs (miRNAs) are a family of short noncoding RNAs (18 to 22 nucleotides) and bind the 3' un-translated region (UTR) of their target genes to post-transcriptionally suppress gene expression. In this study, we report miR-143 is downregulated in rat neurons but high expressed in astrocytes cells. In vivo middle cerebral artery occlusion (MCAO) and ex vivo oxygen-glucose deprivation (OGD) results showed miR-143 was significantly induced by ischemia injury...
May 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28515149/pyruvate-kinase-inhibits-proliferation-during-postnatal-cerebellar-neurogenesis-and-suppresses-medulloblastoma-formation
#2
Katherine Tech, Andrey P Tikunov, Hamza Farooq, A Sorana Morrissy, Jessica Meidinger, Taylor Fish, Sarah C Green, Hedi Liu, Yisu Li, Andrew J Mungall, Richard A Moore, Yussanne Ma, Steven Jm Jones, Marco A Marra, Matthew G Vander Heiden, Michael D Taylor, Jeffrey MacDonald, Timothy R Gershon
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic glycolysis is required for the regulated proliferation of cerebellar granule neuron progenitors (CGNPs), and for the growth of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via deletion of Hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts medulloblastoma growth. Here, we assessed whether disrupting Pyruvate kinase-M (Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP metabolism, proliferation and tumorigenesis...
May 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28498475/targeting-hexokinase-2-inhibition-promotes-radiosensitization-in-hpv16%C3%A2-e7-induced-cervical-cancer-and-suppresses-tumor-growth
#3
Yuan Liu, Tracy Murray-Stewart, Robert A Casero, Ioannis Kagiampakis, Lihua Jin, Jiawen Zhang, Huihui Wang, Qi Che, Huan Tong, Jieqi Ke, Feizhou Jiang, Fangyuan Wang, Xiaoping Wan
In order to improve the sensitivity of cervical cancer cells to irradiation therapy, we targeted hexokinase 2 (HK2), the first rate-limiting enzyme of glycolysis, and explore its role in cervical cancer cells. We suppressed HK2 expression and/or function by shRNA and/or metformin and found HK2 inhibition enhanced cells apoptosis with accelerating expression of cleaved PARP and caspase-3. HK2 inhibition also induced much inferior proliferation of cervical cancer cells both in vitro and in vivo with diminishing expression of mTOR, MIB and MGMT...
May 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28483437/4-phenyl-butyric-acid-increases-particulate-hexokinase-activity-and-protects-against-ros-injury-in-l6-myotubes
#4
Michele Hinerasky da Silva, Flavia Letícia Martins Peçanha, Aline Machado de Oliveira, Wagner Seixas da-Silva
Hexokinase (HK) is the first enzyme in the glycolytic pathway and is responsible for glucose phosphorylation and fixation into the cell. HK (HK-II) is expressed in skeletal muscle and can be found in the cytosol or bound mitochondria, where it can protect cells against insults such as oxidative stress. 4-Phenyl butyric acid (4-PBA) is a chemical chaperone that inhibits endoplasmic reticulum stress and contributes to the restoring of glucose homeostasis. AIMS: Here, we decided to investigate whether HK activity and its interaction with mitochondria could be a target of 4-PBA action...
May 5, 2017: Life Sciences
https://www.readbyqxmd.com/read/28478957/sirt6-regulated-nucleosomal-occupancy-affects-hexokinase-2-expression
#5
Piyushi Gupta, Touseef Sheikh, Ellora Sen
To understand the molecular association between inflammation and dysregulated metabolism in glioblastoma, the effect of IL-1β on Hexokinase 2 (HK2) expression was investigated. IL-1β induced HK2 expression was accompanied by heightened SIRT6 and MZF1 levels. IL-1β mediated overall decrease in chromatin compactness on HK2 promoter involved diminished nucleosomal occupancy around the most labile region bearing MZF1 sites. Importantly, SIRT6 and MZF1 served as negative regulators of HK2. Ectopic SIRT6 induced formation and recruitment of MZF1-SIRT6 complex to MZF1 site was concomitant with increased nucleosomal occupancy...
May 4, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28471448/mir-1-suppresses-tumor-cell-proliferation-in-colorectal-cancer-by-inhibition-of-smad3-mediated-tumor-glycolysis
#6
Wanfu Xu, Zijing Zhang, Kejian Zou, Yang Cheng, Min Yang, Huan Chen, Hongli Wang, Junhong Zhao, Peiyu Chen, Liying He, Xinwen Chen, Lanlan Geng, Sitang Gong
Aberrant expression of microRNA (miR)-1 has been observed in many human malignancies. However, the function and underlying mechanism of miR-1 remains elusive. To address the specific role of miR-1 in tumor glycolysis using the gain- or loss-of-function studies. Metabolic studies combined with gene expression analysis were performed in vitro and in vivo. We demonstrated aberrant expression of miR-1 in aerobic glycolysis, the Warburg effect, in cancer cells. MiR-1 suppressed aerobic glycolysis and tumor cell proliferation via inactivation of Smad3 and targeting HIF-1α, leading to reduce HK2 and MCT4 expression, which illustrated a novel pathway to mediate aerobic glycolysis in cancer cells...
May 4, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28467822/fgf-dependent-metabolic-control-of-vascular-development
#7
Pengchun Yu, Kerstin Wilhelm, Alexandre Dubrac, Joe K Tung, Tiago C Alves, Jennifer S Fang, Yi Xie, Jie Zhu, Zehua Chen, Frederik De Smet, Jiasheng Zhang, Suk-Won Jin, Lele Sun, Hongye Sun, Richard G Kibbey, Karen K Hirschi, Nissim Hay, Peter Carmeliet, Thomas W Chittenden, Anne Eichmann, Michael Potente, Michael Simons
Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are important to these processes. Although much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism, little is understood about the role of fibroblast growth factors (FGFs) in this context...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28448866/function-of-microrna-143-in-different-signal-pathways-in-cancer-new-insights-into-cancer-therapy
#8
REVIEW
Leila Karimi, Behzad Mansoori, Dariush Shanebandi, Ali Mohammadi, Mahyar Aghapour, Behzad Baradaran
MicroRNAs (miRNAs) are small non-coding RNAs which participate in the post-transcriptional regulation of gene expression. They play important roles in cellular events such as growth and differentiation. Deregulation of miRNAs is frequently evident in human cancers where their aberrant expression is associated with uncontrolled proliferation, metastasis, impaired cell cycle and DNA damage response. The miRNAs are important in cancer as ∼50% of miRNA genes are located in cancer-associated regions such as fragile sites of genome...
April 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28445971/stat3-regulates-glycolysis-via-targeting-hexokinase-2-in-hepatocellular-carcinoma-cells
#9
Man Li, Rui Jin, Weihua Wang, Tieying Zhang, Jiao Sang, Na Li, Qunying Han, Wenxuan Zhao, Chunyan Li, Zhengwen Liu
Signal transducer and activator of transcription 3 (STAT3) and hexokinase 2 (HK2) are involved in hepatocellular carcinoma (HCC). Deregulation of cellular energetics involving an increase in glycolysis is a characteristic of HCC. This study examined whether STAT3 regulates HCC glycolysis through the HK2 pathway in HCC cells. Human HCC cell lines HepG2 and Hep3B cells were transfected with pcDNA3.1(+)-EGFP-STAT3, STAT3 siRNA and HK2 siRNA, respectively, or treated with rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), and the effects on STAT3 and HK2 expression and cell glycolysis were determined...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445931/high-glucose-induces-apoptosis-via-upregulation-of-bim-expression-in-proximal-tubule-epithelial-cells
#10
Xiao-Qian Zhang, Jian-Jun Dong, Tian Cai, Xue Shen, Xiao-Jun Zhou, Lin Liao
Diabetic nephropathy is the primary cause of end-stage renal disease. Apoptosis of tubule epithelial cells is a major feature of diabetic nephropathy. The mechanisms of high glucose (HG) induced apoptosis are not fully understood. Here we demonstrated that, HG induced apoptosis via upregulating the expression of proapoptotic Bcl-2 homology domain 3 (BH3)-only protein Bim protein, but not bring a significant change in the baseline level of autophagy in HK2 cells. The increase of Bim expression was caused by the ugregulation of transcription factors, FOXO1 and FOXO3a...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28433696/foxc2-positively-regulates-yap-signaling-and-promotes-the-glycolysis-of-nasopharyngeal-carcinoma
#11
Lijuan Song, Hongbo Tang, Wenjing Liao, Xinggu Luo, Yanmei Li, Tao Chen, Xiaowen Zhang
YAP signaling has been reported to be dysregulated in numerous cancer types. However, its roles in nasopharyngeal carcinoma (NPC) are poorly understood. Although several studies have shown that FOXC2 promotes the progression of NPC, the underlying molecular mechanism remains largely unknown. Here, we have shown that FOXC2 interacted with YAP and TEAD, and activated YAP signaling. Furthermore, FOXC2-YAP signaling positively regulated the expression of Hexokinase 2 (HK2) and promoted the glycolysis. Moreover, the inhibitor of HK2, 3-BrPA effectively inhibited the tumorigenesis of NPC cells in vitro and in vivo...
April 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28427443/benserazide-a-dopadecarboxylase-inhibitor-suppresses-tumor-growth-by-targeting-hexokinase-2
#12
Wei Li, Mengzhu Zheng, Shuangping Wu, Suyu Gao, Mei Yang, Zhimei Li, Qiuxia Min, Weiguang Sun, Lixia Chen, Guangya Xiang, Hua Li
BACKGROUND: Hexokinase (HK) is the rate-limiting enzyme in the first reaction of glycolysis. And Hexokinase 2 (HK2) is most closely related to malignant tumor which expresses at higher level compared with normal cells. HK2 plays a pivotal role in tumor initiation and maintenance, which provides a new target for cancer therapy. METHODS: Structure-based virtual ligand screening was used in hit identification from ZINC Drug Database. Microscale thermophoresis assay was performed to evaluate the binding affinity...
April 20, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28427230/deguelin-inhibits-non-small-cell-lung-cancer-via-down-regulating-hexokinases-ii-mediated-glycolysis
#13
Wei Li, Feng Gao, Xiaoqian Ma, Ruike Wang, Xin Dong, Wei Wang
Hexokinases II (HK2) is a hub in the regulation of cancer cell glycolysis. Here we reported deguelin, a natural compound which has been studied in various tumor types, has a profound anti-tumor effect on human non-small cell lung cancer (NSCLC) via directly down-regulating of glycolysis. In NSCLC cell lines and primary NSCLC tissue, we found HK2 is overexpressed. Deguelin treatment markedly inhibited anchorage-dependent and independent growth of NSCLC cell lines. We revealed that deguelin exposure impaired glucose metabolism by inhibiting Akt-mediated Hexokinase II expression, overexpression of constitutively activated Akt1 substantially rescued deguelin-induced glycolysis suppression...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425456/salt-suppresses-ifn%C3%AE-inducible-chemokines-through-the-ifn%C3%AE-jak1-stat1-signaling-pathway-in-proximal-tubular-cells
#14
Yohei Arai, Daiei Takahashi, Kenichi Asano, Masato Tanaka, Mayumi Oda, Shigeru B H Ko, Minoru S H Ko, Shintaro Mandai, Naohiro Nomura, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
The mechanisms of immunoactivation by salt are now becoming clearer. However, those of immunosuppression remain unknown. Since clinical evidence indicates that salt protects proximal tubules from injury, we investigated mechanisms responsible for salt causing immunosuppression in proximal tubules. We focused on cytokine-related gene expression profiles in kidneys of mice fed a high salt diet using microarray analysis and found that both an interferon gamma (IFNγ) inducible chemokine, chemokine (C-X-C motif) ligand 9 (CXCL9), and receptor, CXCR3, were suppressed...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424621/activation-of-sirtuin-3-by-silybin-attenuates-mitochondrial-dysfunction-in-cisplatin-induced-acute-kidney-injury
#15
Yin Li, Zengchun Ye, Weiyan Lai, Jialing Rao, Wanbing Huang, Xiaohao Zhang, Ziying Yao, Tanqi Lou
Silybin is a secondary metabolite isolated from the seeds of blessed milk thistle (Silybum marianum) that has anti-inflammatory, antioxidative, antifibrotic, and antitumor properties. Here, we showed that silybin protected against cisplatin-induced acute kidney injury (AKI) by improving mitochondrial function through the regulation of sirtuin 3 (SIRT3) expression. Male SV129 and SIRT3 knockout (KO) mice were administered a single intraperitoneal (i.p.) injection of cisplatin with or without treatment with silybin...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28423489/target-of-obstructive-sleep-apnea-syndrome-merge-lung-cancer-based-on-big-data-platform
#16
Lifeng Li, Jingli Lu, Wenhua Xue, Liping Wang, Yunkai Zhai, Zhirui Fan, Ge Wu, Feifei Fan, Jieyao Li, Chaoqi Zhang, Yi Zhang, Jie Zhao
Based on our hospital database, the incidence of lung cancer diagnoses was similar in obstructive sleep apnea Syndrome (OSAS) and hospital general population; among individual with a diagnosis of lung cancer, the presence of OSAS was associated with an increased risk for mortality. In the gene expression and network-level information, we revealed significant alterations of molecules related to HIF1 and metabolic pathways in the hypoxic-conditioned lung cancer cells. We also observed that GBE1 and HK2 are downstream of HIF1 pathway important in hypoxia-conditioned lung cancer cell...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420760/novel-lnc-rna-regulated-by-hif-1-inhibits-apoptotic-cell-death-in-the-renal-tubular-epithelial-cells-under-hypoxia
#17
Imari Mimura, Yosuke Hirakawa, Yasuharu Kanki, Natsuki Kushida, Ryo Nakaki, Yutaka Suzuki, Tetsuhiro Tanaka, Hiroyuki Aburatani, Masaomi Nangaku
Chronic tubulointerstitial hypoxia plays an important role as the final common pathway to end-stage renal disease. HIF-1 (hypoxia-inducible factor-1) is a master transcriptional factor under hypoxia, regulating downstream target genes. Genome-wide analysis of HIF-1 binding sites using high-throughput sequencers has clarified various kinds of downstream targets and made it possible to demonstrate the novel roles of HIF-1. Our aim of this study is to identify novel HIF-1 downstream epigenetic targets which may play important roles in the kidney...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28415659/poor-prognosis-of-hexokinase-2-overexpression-in-solid-tumors-of-digestive-system-a-meta-analysis
#18
REVIEW
Jiayuan Wu, Liren Hu, Fenping Wu, Lei Zou, Taiping He
Several previous studies have reported the prognostic value of hexokinase 2 (HK2) in digestive system tumors. However, these studies were limited by the small sample sizes and the results were inconsistent among them. Therefore, we conducted a meta-analysis based on 15 studies with 1932 patients to assess the relationship between HK2 overexpression and overall survival (OS) of digestive system malignancies. The relationship of HK2 and clinicopathological features was also evaluated. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence intervals (CI) were calculated to estimate the effect size...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410220/reprogramming-induced-by-isoliquiritigenin-diminishes-melanoma-cachexia-through-mtorc2-akt-gsk3%C3%AE-signaling
#19
Xiao-Yu Chen, De-Fang Li, Ji-Chun Han, Bo Wang, Zheng-Ping Dong, Li-Na Yu, Zhao-Hai Pan, Chuan-Jun Qu, Ying Chen, Shi-Guo Sun, Qiu-Sheng Zheng
Isoliquiritigenin (ISL), a member of the flavonoids, is known to have anti-tumor activity in vitro and in vivo. The effect of ISL on reprogramming in cancer cells, however, remains elusive. In this study, we investigated the effect of ISL on reprogramming in human melanoma A375 cells. ISL (15 μg/ml) significantly inhibited A375 cell proliferation, anchorage independent cell proliferation and G2/M cell cycle arrest after ISL exposure for 24 h. However, there were no significant changes in apoptosis rate. Terminal differentiation indicators (melanin content, melanogenesis mRNA expression, tyrosinase (TYR) activity) were all up-regulated by ISL treatment...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404597/altered-mirna-29-expression-in-type-2-diabetes-influences-glucose-and-lipid-metabolism-in-skeletal-muscle
#20
Julie Massart, Rasmus J O Sjögren, Leonidas S Lundell, Jonathan M Mudry, Niclas Franck, Donal J O'Gorman, Brendan Egan, Juleen R Zierath, Anna Krook
MicroRNAs have emerged as important regulators of glucose and lipid metabolism in several tissues, however, their role in skeletal muscle remains poorly characterized. We determined the effects of the miR-29 family on glucose and lipid metabolism, and insulin responsiveness in skeletal muscle. We provide evidence that miR-29a and miR-29c are increased in skeletal muscle from type 2 diabetic patients and decreased following endurance training in healthy young men and in rats. In primary human skeletal muscle cells, inhibition and overexpression strategies demonstrate that miR-29a and miR-29c regulate glucose uptake and insulin-stimulated glucose metabolism...
April 12, 2017: Diabetes
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