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https://www.readbyqxmd.com/read/28219903/myc-driven-inhibition-of-the-glutamate-cysteine-ligase-promotes-glutathione-depletion-in-liver-cancer
#1
Brittany Anderton, Roman Camarda, Sanjeev Balakrishnan, Asha Balakrishnan, Rebecca A Kohnz, Lionel Lim, Kimberley J Evason, Olga Momcilovic, Klaus Kruttwig, Qiang Huang, Guowang Xu, Daniel K Nomura, Andrei Goga
How MYC reprograms metabolism in primary tumors remains poorly understood. Using integrated gene expression and metabolite profiling, we identify six pathways that are coordinately deregulated in primary MYC-driven liver tumors: glutathione metabolism; glycine, serine, and threonine metabolism; aminoacyl-tRNA biosynthesis; cysteine and methionine metabolism; ABC transporters; and mineral absorption. We then focus our attention on glutathione (GSH) and glutathione disulfide (GSSG), as they are markedly decreased in MYC-driven tumors...
February 20, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28217257/regulation-of-hepatic-microrna-expression-by-hepatocyte-nuclear-factor-4-alpha
#2
Hong Lu, Xiaohong Lei, Jerry Liu, Curtis Klaassen
AIM: To uncover the role of hepatocyte nuclear factor 4 alpha (HNF4α) in regulating hepatic expression of microRNAs. METHODS: Microarray and real-time PCR were used to determine hepatic expression of microRNAs in young-adult mice lacking Hnf4α expression in liver (Hnf4α-LivKO). Integrative genomics viewer software was used to analyze the public chromatin immunoprecipitation-sequencing datasets for DNA-binding of HNF4α, RNA polymerase-II, and histone modifications to loci of microRNAs in mouse liver and human hepatoma cells...
February 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28215541/evaluation-of-a-combinational-use-of-serum-micrornas-as-biomarkers-for-liver-diseases
#3
Ping Xu, Anliang Guo, Junchi Xu, Jianer Yao, Hui Chen, Fengping Wang, Chuanwu Zhu
Circulating microRNAs (miRNA) have been widely recognized as a novel noninvasive biomarker in a variety of physiological and pathological conditions. In order to assess the sensitivity and reliability of potential miRNAs as diagnostic markers for liver disease related to viral infection, alcohol abuse, or chemical exposure, we collected serum samples from 326 participants and evaluated the single and combination diagnostic values of three serum miRNAs (miR-122, miR-125b, miR-192) compared with a conventional marker ALT...
February 16, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28211229/serum-micrornas-as-predictors-for-liver-fibrosis-staging-in-hepatitis-c-virus-associated-chronic-liver-disease-patients
#4
Olfat G Shaker, Mahmoud A Senousy
Accurate staging of liver fibrosis is important for clinical decision making and personalized management. Liver fibrosis is influenced by patients' genomics, including IFNL3 genotype and microRNA expression. However, incorporating microRNAs into fibrosis prediction algorithms has not been investigated. We examined the potential of 8 selected serum microRNAs; miR-122, miR-126, miR-129, miR-199a, miR-155, miR-203a, miR-221, and miR-223 as non-invasive biomarkers to stage liver fibrosis in HCV-associated chronic liver disease (HCV-CLD)...
February 17, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28208010/circulating-plasma-and-exosomal-micrornas-as-indicators-of-drug-induced-organ-injury-in-rodent-models
#5
Young-Eun Cho, Sang-Hyun Kim, Byung-Heon Lee, Moon-Chang Baek
This study was performed to evaluate whether microRNAs (miRNAs) in circulating exosomes may serve as biomarkers of drug-induced liver, kidney, or muscle-injury. Quantitative PCR analyses were performed to measure the amounts of liver-specific miRNAs (miR-122, miR-192, and miR-155), kidney-specific miR-146a, or muscle-specific miR-206 in plasma and exosomes from mice treated with liver, kidney or muscle toxicants. The levels of liver-specific miRNAs in circulating plasma and exosomes were elevated in acetaminophen-induced liver injury and returned to basal levels by treatment with antioxidant N-acetyl-cysteine...
February 17, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28199304/adipose-derived-circulating-mirnas-regulate-gene-expression-in-other-tissues
#6
Thomas Thomou, Marcelo A Mori, Jonathan M Dreyfuss, Masahiro Konishi, Masaji Sakaguchi, Christian Wolfrum, Tata Nageswara Rao, Jonathon N Winnay, Ruben Garcia-Martin, Steven K Grinspoon, Phillip Gorden, C Ronald Kahn
Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue-brown especially-into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28193507/identification-of-organ-tissue-types-and-skin-from-forensic-samples-by-microrna-expression-analysis
#7
Eva Sauer, Antje Extra, Philipp Cachée, Cornelius Courts
The identification of organ tissues in traces recovered from scenes and objects with regard to violent crimes involving serious injuries can be of considerable relevance in forensic investigations. Molecular genetic approaches are provably superior to histological and immunological assays in characterizing organ tissues, and micro-RNAs (miRNAs), due to their cell type specific expression patterns and stability against degradation, emerged as a promising molecular species for forensic analyses, with a range of tried and tested indicative markers...
February 5, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28192189/mir-425-regulates-inflammatory-cytokine-production-in-cd4-t-cells-via-n-ras-upregulation-in-primary-biliary-cholangitis
#8
Ryo Nakagawa, Ryosuke Muroyama, Chisato Saeki, Kaku Goto, Yoshimi Kaise, Kazuhiko Koike, Masanori Nakano, Yasuo Matsubara, Keiko Takano, Sayaka Ito, Masayuki Saruta, Naoya Kato, Mikio Zeniya
BACKGROUND & AIM: Primary biliary cholangitis (PBC) is an autoimmune liver disease of unknown pathogenesis. Consequently, therapeutic targets for PBC have yet to be identified. Because CD4(+) T cells play a pivotal role in immunological dysfunction observed in PBC, we analysed microRNA (miRNA) and mRNA expression in CD4(+) T cells to investigate PBC pathogenesis and identify novel therapeutic targets. METHODS: We performed integral miRNA and mRNA analysis of 14 PBC patients and 10 healthy controls using microarray and quantitative real time polymerase chain reaction (qRT-PCR) with gene set enrichment analysis...
February 9, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28192178/identification-and-characterization-of-the-expression-profile-of-the-micrornas-in-the-amazon-species-colossoma-macropomum-by-next-generation-sequencing
#9
Fátima Gomes, Luciana Watanabe, Sérgio Nozawa, Layanna Oliveira, Jedson Cardoso, João Vianez, Márcio Nunes, Horacio Schneider, Iracilda Sampaio
Colossoma macropomum is a resistant species native of Amazonas and Orinoco river basins. It is regarded as the second largest finfish of Solimões and Amazon rivers, representing a major fishery resource in Amazonas and an important species in tropical aquaculture. MicroRNAs are non-coding endogenous riboregulators of nearly 22 nucleotides that play a key role in post-transcriptional gene regulation of several organisms. We analyzed samples of liver and skin from specimens of C. macropomum using next generation sequencing...
February 10, 2017: Genomics
https://www.readbyqxmd.com/read/28185365/circrnas-biogenesis-properties-roles-and-their-relationships-with-liver-diseases-running-title-circular-rnas-and-liver-diseases
#10
REVIEW
Ting Yao, Qingqing Chen, Liyun Fu, Junming Guo
Circular RNAs (circRNAs) are a class of new found RNA molecules that have a special covalent loop structure without 5' cap and 3' tail. Researchers have found that circRNAs may be generated by intron-pairing-driven or lariat-driven circularization. They are cleared up via extracellular vesicles. They have some advantages such as stable, conservation, tissue specificity and so on. By severing as sponge of microRNAs, interacting with long non-coding RNAs, mRNA, or proteins, circRNAs regulate gene expression at transcriptional and post-transcriptional levels and contribute carcinogenesis...
February 10, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28179883/new-microrna-biomarkers-for-drug-induced-steatosis-and-their-potential-to-predict-the-contribution-of-drugs-to-non-alcoholic-fatty-liver-disease
#11
Mireia López-Riera, Isabel Conde, Laia Tolosa, Ángela Zaragoza, José V Castell, María J Gómez-Lechón, Ramiro Jover
Background and Aims: Drug-induced steatosis is a major reason for drug failure in clinical trials and post-marketing withdrawal; and therefore, predictive biomarkers are essential. These could be particularly relevant in non-alcoholic fatty liver disease (NAFLD), where most patients show features of the metabolic syndrome and are prescribed with combined chronic therapies, which can contribute to fatty liver. However, specific biomarkers to assess the contribution of drugs to NAFLD are lacking. We aimed to find microRNAs (miRNAs) responsive to steatotic drugs and to investigate if they could become circulating biomarkers for drug-induced steatosis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28177765/diosmin-attenuates-radiation-induced-hepatic-fibrosis-via-boosting-ppar-%C3%AE-expression-and-hampering-mir-17-5p-activated-canonical-wnt-%C3%AE-catenin-signaling
#12
Hesham Farouk Hasan, Mohamed Khairy Abdel-Rafei, Shereen Mohamed Galal
BACKGROUND: Liver fibrosis is one of the major complications of upper right quadrant radiotherapy. MicroRNA-17-5p (miR-17-5p) is hypothesized to act as regulator of hepatic stellate cells (HSCs) activation via activation of canonical Wnt/β-catenin pathway. Diosmin (Dios), a citrus bioflavonoid, is known to possess potent antioxidant, anti-inflammatory and anti-apoptotic properties. PURPOSE: To explore molecular mechanisms underlie radiation- induced liver fibrosis and evaluate the possible influence of Dios on miR-17-5p/ Wnt/ β-catenin signaling axis during fibrogenesis provoked by irradiation (IRR) in rats...
November 21, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28174625/sex-and-age-differences-in-the-expression-of-liver-micrornas-during-the-life-span-of-f344-rats
#13
Joshua C Kwekel, Vikrant Vijay, Tao Han, Carrie L Moland, Varsha G Desai, James C Fuscoe
BACKGROUND: Physiological factors such as age and sex have been shown to be risk factors for adverse effects in the liver, including liver diseases and drug-induced liver injury. Previously, we have reported age- and sex-related significant differences in hepatic basal gene expression in rats during the life span that may be related to susceptibility to such adverse effects. However, the underlying mechanisms of the gene expression changes were not fully understood. In recent years, increasing evidence for epigenetic mechanisms of gene regulation has fueled interest in the role of microRNAs (miRNAs) in toxicogenomics and biomarker discovery...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28167956/micrornas-dependent-regulation-of-ppars-in-metabolic-diseases-and-cancers
#14
REVIEW
Dorothea Portius, Cyril Sobolewski, Michelangelo Foti
Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-dependent nuclear receptors, which control the transcription of genes involved in energy homeostasis and inflammation and cell proliferation/differentiation. Alterations of PPARs' expression and/or activity are commonly associated with metabolic disorders occurring with obesity, type 2 diabetes, and fatty liver disease, as well as with inflammation and cancer. Emerging evidence now indicates that microRNAs (miRNAs), a family of small noncoding RNAs, which fine-tune gene expression, play a significant role in the pathophysiological mechanisms regulating the expression and activity of PPARs...
2017: PPAR Research
https://www.readbyqxmd.com/read/28167804/mir-29a-modulates-scd-expression-and-is-regulated-in-response-to-a-saturated-fatty-acids-diet-in-juvenile-gift-oreochromis-niloticus
#15
Jun Qiang, Yi Fan Tao, Jie He, Yi Lan Sun, Pao Xu
MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression by binding to the 3'untranslated region (3'UTR) of the target mRNA. MiRNAs regulate a large variety of genes, including those involved in liver biology and disease. Here, we report for the first time that miR-29a post-transcriptionally regulates stearoyl-CoA desaturase (SCD) by binding to its 3'UTR in genetically improved farmed tilapia (GIFT), Oreochromis niloticus, as shown by a 3'UTR luciferase reporter assay. miR-29a antagomir treatment in vivo resulted in significant up-regulation of SCD expression...
February 6, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28166203/lncrna-hulc-triggers-autophagy-via-stabilizing-sirt1-and-attenuates-the-chemosensitivity-of-hcc-cells
#16
H Xiong, Z Ni, J He, S Jiang, X Li, J He, W Gong, L Zheng, S Chen, B Li, N Zhang, X Lyu, G Huang, B Chen, Y Zhang, F He
Considerable evidences have shown that autophagy has an important role in tumor chemoresistance. However, it is still unknown whether the lncRNA HULC (highly upregulated in liver cancer) is involved in autophagy and chemoresistance of hepatocellular carcinoma (HCC). In this study, we for the first time demonstrated that treatment with antitumor reagents such as oxaliplatin, 5-fluorouracil and pirarubicin (THP) dramatically induced HULC expression and protective autophagy. Silencing of HULC sensitized HCC cells to the three antitumor reagents via inhibiting protective autophagy...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28164635/microrna-122-as-a-novel-non-invasive-marker-of-liver-fibrosis-in-hepatitis-c-virus-patients
#17
Ahmed A S Omran, Khalid S Osman, Hanan M Kamel, Emad A Abdel-Naem, Dalia E El-Deen Hasan
BACKGROUND: Noninvasive evaluation of hepatic fibrosis is a growing scientific effort in medicine and is of particular interest as early diagnosis is important for the timely prevention and treatment of liver fibrosis and cirrhosis. Non-invasive markers of liver fibrosis have recently been developed as an alternative to liver biopsy. Aim of the work: The aim of this study was to assess the diagnostic value of serum microRNA 122 in Egyptian chronic hepatitis C virus infected patients. This may be a useful tool as a non invasive diagnostic test to detect early stages of fibrosis in comparison to 4 non invasive indexes (APRI, Forns, FIB-4, and FI) vs...
July 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28159835/mir-135a-5p-mediated-downregulation-of-protein-tyrosine-phosphatase-receptor-delta-is-a-candidate-driver-of-hcv-associated-hepatocarcinogenesis
#18
Nicolaas Van Renne, Armando Andres Roca Suarez, Francois H T Duong, Claire Gondeau, Diego Calabrese, Nelly Fontaine, Amina Ababsa, Simonetta Bandiera, Tom Croonenborghs, Nathalie Pochet, Vito De Blasi, Patrick Pessaux, Tullio Piardi, Daniele Sommacale, Atsushi Ono, Kazuaki Chayama, Masashi Fujita, Hidewaki Nakagawa, Yujin Hoshida, Mirjam B Zeisel, Markus H Heim, Thomas F Baumert, Joachim Lupberger
BACKGROUND AND AIMS: HCV infection is a leading risk factor of hepatocellular carcinoma (HCC). However, even after viral clearance, HCC risk remains elevated. HCV perturbs host cell signalling to maintain infection, and derailed signalling circuitry is a key driver of carcinogenesis. Since protein phosphatases are regulators of signalling events, we aimed to identify phosphatases that respond to HCV infection with relevance for hepatocarcinogenesis. METHODS: We assessed mRNA and microRNA (miRNA) expression profiles in primary human hepatocytes, liver biopsies and resections of patients with HCC, and analysed microarray and RNA-seq data from paired liver biopsies of patients with HCC...
February 3, 2017: Gut
https://www.readbyqxmd.com/read/28154773/role-of-micrornas-in-inflammation-associated-liver-cancer
#19
Lin Huan, Lin-Hui Liang, Xiang-Huo He
Liver cancer, primarily hepatocellular carcinoma (HCC), is a major cause of cancer-related death worldwide. HCC is a suitable model of inflammation-induced cancer because more than 90% of HCC cases are caused by liver damage and chronic inflammation. Several inflammatory response pathways, such as NF-κB and JAK/STAT3 signaling pathways, play roles in the crosstalk between inflammation and HCC. MicroRNAs (miRNAs) are evolutionarily conserved, short endogenous, non-coding single-stranded RNAs that are involved in various biological and pathological processes by regulating gene expression and protein translation...
December 2016: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28153841/cholic-acid-feeding-leads-to-increased-cyp2d6-expression-in-cyp2d6-humanized-mice
#20
Xian Pan, Rebecca Kent, Kyoung-Jae Won, Hyunyoung Jeong
Cytochrome P450 2D6 (CYP2D6) is a major drug-metabolizing enzyme, but factors governing transcriptional regulation of its expression remain poorly understood. Based on previous reports of small heterodimer partner (SHP) playing an important role as a transcriptional repressor of CYP2D6 expression, here we investigated how a known upstream regulator of SHP expression, namely cholestasis triggered by cholic acid (CA) feeding in mice, can lead to altered CYP2D6 expression. To this end, CYP2D6-humanized (Tg-CYP2D6) mice were fed with CA-supplemented or control diet for 14 days, and hepatic expression of multiple genes was examined...
February 2, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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