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https://www.readbyqxmd.com/read/28448866/function-of-microrna-143-in-different-signal-pathways-in-cancer-new-insights-into-cancer-therapy
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
March 6, 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
#7
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
#8
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
#9
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
#10
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
#11
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...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410220/reprogramming-induced-by-isoliquiritigenin-diminishes-melanoma-cachexia-through-mtorc2-akt-gsk3%C3%AE-signaling
#12
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
#13
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
https://www.readbyqxmd.com/read/28398674/melatonin-protects-cardiac-microvasculature-against-ischemia-reperfusion-injury-via-suppression-of-mitochondrial-fission-vdac1-hk2-mptp-mitophagy-axis
#14
Hao Zhou, Ying Zhang, Shunying Hu, Chen Shi, Pingjun Zhu, Qiang Ma, Qinhua Jin, Feng Cao, Feng Tian, Yundai Chen
The cardiac microvascular system, which is primarily composed of monolayer endothelial cells, is the site of blood supply and nutrient exchange to cardiomyocytes. However, microvascular ischemia/reperfusion injury (IRI) following percutaneous coronary intervention is a woefully neglected topic and few strategies are available to reverse such pathologies. Here, we studied the effects of melatonin on microcirculation IRI and elucidated the underlying mechanism. Melatonin markedly reduced infarcted area, improved cardiac function, restored blood flow and lower microcirculation perfusion defects...
April 11, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28391169/hypoxia-induced-extracellular-vesicles-mediate-protection-of-remote-ischemic-preconditioning-for-renal-ischemia-reperfusion-injury
#15
Guangyuan Zhang, Yu Yang, Yeqing Huang, Lei Zhang, Zhixin Ling, Yingjian Zhu, Feng Wang, Xiangyu Zou, Ming Chen
Remote ischemic preconditioning (rIPC) is a reliable strategy for prevention of injury to various organs. However the mechanism by which it does so is still unclear. In the present study, serum and EVs isolated from ischemic preconditioned right renal venous perfusates were injected into rats with ischemia-reperfusion-injured kidneys immediately after reperfusion. The animals were killed 24h later. Tubular scores and renal function were tested to evaluate the therapeutic effects. To further explore the underlying mechanism, HK-2 cells derived EVs under hypoxia were also administrated to rats with left kidney IRI...
April 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28388590/integrated-expression-profiles-analysis-reveals-novel-predictive-biomarker-in-pancreatic-ductal-adenocarcinoma
#16
Hongzhe Li, Xinjing Wang, Yuan Fang, Zhen Huo, Xiongxiong Lu, Xi Zhan, Xiaxin Deng, Chenghong Peng, Baiyong Shen
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal human malignant tumor, with a dismal 5-year survival rate of less than 5%. The lack of specific symptoms at early tumor stages and the paucity of biomarkers contribute to the poor diagnosis of pancreatic ductal adenocarcinoma. To improve prognosis, a screening biomarker for early diagnosis of pancreatic cancer is in urgent need. We searched the databases of expression profiling by array on GEO, aiming at comparing gene expression profile of matched pairs of pancreatic tumor and adjacent non-tumor tissues, and we screen out 4 suitable series of gene expression microarray data ("GSE15471", "GSE18670", "GSE28735" and "GSE58561")...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28387640/fructose-1-6-bisphosphatase-1-reduces-18-f-fdg-uptake-in-hepatocellular-carcinoma
#17
Ruohua Chen, Jiajin Li, Xiang Zhou, Jianjun Liu, Gang Huang
Purpose To determine whether fructose 1,6-bisphosphatase 1 (FBP1) expression is associated with fluorine 18 ((18)F) fluorodeoxyglucose (FDG) accumulation in patients with hepatocellular carcinoma (HCC) and to investigate how FBP1 expression and (18)F FDG uptake are related to tumor differentiation grade and metabolism and whether the molecular mechanism involves hypoxia-inducible factor 1-α (HIF1A) transcriptional activity. Materials and Methods This retrospective study was approved by the institutional review board with informed consent...
April 6, 2017: Radiology
https://www.readbyqxmd.com/read/28387228/calcium-oxalate-crystals-and-oxalate-induce-an-epithelial-to-mesenchymal-transition-in-the-proximal-tubular-epithelial-cells-contribution-to-oxalate-kidney-injury
#18
Marcia Bastos Convento, Edson Andrade Pessoa, Edgar Cruz, Maria Aparecida da Glória, Nestor Schor, Fernanda Teixeira Borges
TGF-β1 is the main mediator of epithelial-to-mesenchymal transition (EMT). Hyperoxaluria induces crystalluria, interstitial fibrosis, and progressive renal failure. This study analyzed whether hyperoxaluria is associated with TGF-β1 production and kidney fibrosis in mice and if oxalate or calcium oxalate (CaOx) could induce EMT in proximal tubule cells (HK2) and therefore contribute to the fibrotic process. Hyperoxaluria was induced by adding hydroxyproline and ethylene glycol to the mice's drinking water for up to 60 days...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28350132/a-new-facet-of-ndrg1-in-pancreatic-ductal-adenocarcinoma-suppression-of-glycolytic-metabolism
#19
Wensheng Liu, Bo Zhang, Qiangsheng Hu, Yi Qin, Wenyan Xu, Si Shi, Chen Liang, Qingcai Meng, Jinfeng Xiang, Dingkong Liang, Shunrong Ji, Jiang Liu, Pengfei Hu, Liang Liu, Chen Liu, Jiang Long, Quanxing Ni, Xianjun Yu, Jin Xu
N-myc downstream-regulated gene 1 (NDRG1) is known as tumor/metastasis suppressor in a variety of cancers including pancreas, being involved in angiogenesis, cancer growth and metastasis. However, the precise molecular mechanism how NDRG1 exerts its inhibitory function in pancreatic cancer remains unclear. In this investigation, we demonstrated that K-Ras plays a vital role in modulating NDRG1 protein level in PDAC cancer cells in vitro, which is mediated through ERK signaling. Noteworthy, K-Ras downstream Akt/mTOR signaling is inhibited upon NDRG1 overexpression, resulting in decease of HIF1α level...
March 28, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28336462/the-molecular-mechanisms-of-androgen-receptor-in-nephrolithiasis
#20
Ziyu Fang, Yonghan Peng, Ling Li, Min Liu, Zeyu Wang, Shaoxiong Ming, Wenhui Zhang, Xiaofeng Gao
OBJECTIVES: This study aimed to investigate the molecular mechanisms of androgen receptor (AR) in nephrolithiasis. METHODS: Human kidney 2(HK-2) cells were transfected with Lentiviruses expressing AR (DEC-AR), shRNA targeting AR (sh-AR) or the empty vector control using the pLEX lentiviral vector system. The expression levels of AR were measured by qRT-PCR at 72h postinfection, and cells under different treatments were collected for microarray analysis. Differentially expressed genes (DEGs) were identified using Student's t-test...
June 15, 2017: Gene
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