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https://www.readbyqxmd.com/read/28095325/peroxisome-proliferator-activated-receptor-%C3%AE-activation-inhibits-liver-growth-through-mir-122-mediated-downregulation-of-cmyc
#1
Andrei A Yarushkin, Yuliya A Kazantseva, Vyacheslav S Kobelev, Yuliya A Pustylnyak, Vladimir O Pustylnyak
Although NR1C3 agonists inhibit cell growth, the molecular mechanism of their action has not been thoroughly characterized to date. A recent study demonstrated that NR1C3 can regulate miR-122 by binding to its promoter. Given that miR-122 can indirectly regulate cMyc-mediated promitogenic signaling by targeting E2f1, we hypothesized that NR1C3 activation inhibits hepatocyte proliferation through miR-122-mediated cMyc downregulation. In the present study, we examined if liver hyperplasia induced by a strong chemical mitogen for the liver, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of NR1I3, can be repressed by NR1C3 activation through miR-122 upregulation...
January 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28093198/mild-hypothermia-pretreatment-protects-hepatocytes-against-ischemia-reperfusion-injury-via-down-regulating-mir-122-and-igf-1r-akt-pathway
#2
Qi Xiao, Qi-Fa Ye, Wei Wang, Bi-Qi Fu, Zhi-Ping Xia, Zhong-Zhong Liu, Xing-Jian Zhang, Yan-Feng Wang
BACKGROUND: Mild hypothermia has been well known as an effective way to reduce ischemia reperfusion injury (IRI), while the mechanisms are still unclear. More and more evidences have indicated that miRNAs should been involved in the regulation of IRI and expecially some miRNAs have shown temp-responsiveness for temperature variation. Therefore, the role of miR-122 in mild hypothermia pretreatment after IRI was investigated. METHODS: We established a LO2 cell anoxia-reoxygenation injury model to simulate liver IRI...
January 13, 2017: Cryobiology
https://www.readbyqxmd.com/read/28087069/safety-tolerability-and-antiviral-effect-of-rg-101-in-patients-with-chronic-hepatitis-c-a-phase-1b-double-blind-randomised-controlled-trial
#3
Meike H van der Ree, J Marleen de Vree, Femke Stelma, Sophie Willemse, Marc van der Valk, Svend Rietdijk, Richard Molenkamp, Janke Schinkel, Ad C van Nuenen, Ulrich Beuers, Salah Hadi, Marten Harbers, Eva van der Veer, Kai Liu, John Grundy, Amy K Patick, Adam Pavlicek, Jacqueline Blem, Michael Huang, Paul Grint, Steven Neben, Neil W Gibson, Neeltje A Kootstra, Hendrik W Reesink
BACKGROUND: miR-122 is an important host factor for hepatitis C virus (HCV) replication. The aim of this study was to assess the safety and tolerability, pharmacokinetics, and antiviral effect of a single dose of RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122, in patients with chronic HCV infection with various genotypes. METHODS: In this randomised, double-blind, placebo-controlled, multicentre, phase 1B study, patients were randomly assigned to RG-101 or placebo (7:1)...
January 10, 2017: Lancet
https://www.readbyqxmd.com/read/28070111/a-monkey-model-of-acetaminophen-induced-hepatotoxicity-phenotypic-similarity-to-human
#4
Satoshi Tamai, Takuma Iguchi, Noriyo Niino, Kei Mikamoto, Ken Sakurai, Ayako Sayama, Hitomi Shimoda, Wataru Takasaki, Kazuhiko Mori
Species-specific differences in the hepatotoxicity of acetaminophen (APAP) have been shown. To establish a monkey model of APAP-induced hepatotoxicity, which has not been previously reported, APAP at doses up to 2,000 mg/kg was administered orally to fasting male and female cynomolgus monkeys (n = 3-5/group) pretreated intravenously with or without 300 mg/kg of the glutathione biosynthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO). In all the animals, APAP at 2,000 mg/kg with BSO but not without BSO induced hepatotoxicity, which was characterized histopathologically by centrilobular necrosis and vacuolation of hepatocytes...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28052756/small-rna-sequencing-of-cryopreserved-semen-from-single-bull-revealed-altered-mirnas-and-pirnas-expression-between-high-and-low-motile-sperm-populations
#5
E Capra, F Turri, B Lazzari, P Cremonesi, T M Gliozzi, I Fojadelli, A Stella, F Pizzi
BACKGROUND: Small RNAs present in bovine ejaculate can be linked to sperm abnormalities and fertility disorders. At present, quality parameters routinely used in semen evaluation are not fully reliable to predict bull fertility. In order to provide additional quality measurements for cryopreserved semen used for breeding, a method based on deep sequencing of sperm microRNA (miRNA) and Piwi-interacting RNA (piRNA) from individual bulls was developed. To validate our method, two populations of spermatozoa isolated from high and low motile fractions separated by Percoll were sequenced, and their small RNAs content characterized...
January 4, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28032211/estimation-of-the-human-postmortem-interval-using-an-established-rat-mathematical-model-and-multi-rna-markers
#6
Ye-Hui Lv, Jian-Long Ma, Hui Pan, Yan Zeng, Li Tao, Heng Zhang, Wen-Can Li, Kai-Jun Ma, Long Chen
In our previous study, a R code-based mathematical model using RNA degradation patterns was developed for PMI determination in rat brain specimens. However, the postmortem changes of RNA are much more complicated in real cases, and there is still a huge challenge in efficiently applying information in animal data to real cases. In the present study, different RNA markers in both rat and human tissues were collected to screen valid biomarkers and the corresponding mathematical models were established and validated...
December 28, 2016: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/28008821/cooperative-enhancement-of-translation-by-two-adjacent-microrna-122-argonaute-2-complexes-binding-to-the-5%C3%A2-untranslated-region-of-hepatitis-c-virus-rna
#7
Anika Nieder-Röhrmann, Nadia Dünnes, Gesche K Gerresheim, Lyudmila A Shalamova, Andreas Herchenröther, Michael Niepmann
The liver-specific microRNA-122 (miR-122) binds to two conserved binding sites in the 5´-untranslated region (5´UTR) of Hepatitis C Virus (HCV) RNA. This binding was reported to enhance HCV RNA replication, translation and stability. We have analyzed binding of miR-122/Argonaute 2 (Ago2) complexes to these sites using anti-Ago2-co-immunoprecipitation of radioactively labeled HCV RNAs along with ectopic miR-122 in HeLa cells. Our results show that the miR-122 target sites can be addressed separately. When both target sites were addressed simultaneously, we observed a synergistic binding of both miR/Ago2 complexes...
December 23, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27980102/blocking-the-ccl2-ccr2-axis-using-ccl2-neutralizing-antibody-is-an-effective-therapy-for-hepatocellular-cancer-in-a-mouse-model
#8
Kun-Yu Teng, Jianfeng Han, Xiaoli Zhang, Shu-Hao Hsu, Shun He, Nissar Wani, Juan Barajas, Linda A Snyder, Wendy L Frankel, Michael A Caligiuri, Samson T Jacob, Jianhua Yu, Kalpana Ghoshal
Hepatocellular carcinoma (HCC), a deadly disease, commonly arises in the setting of chronic inflammation. C-C motif chemokine ligand2 (CCL2/MCP1), a chemokine that recruits CCR2-positive immune cells to promote inflammation, is highly upregulated in HCC patients. Here, we examined the therapeutic efficacy of CCL2-CCR2 axis inhibitors against hepatitis and HCC in the miR-122 knockout (aka KO) mouse model. This mouse model displays upregulation of hepatic CCL2 expression, which correlates with hepatitis that progress to HCC with age...
December 15, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27978773/a-longitudinal-assessment-of-mir-122-and-gldh-as-biomarkers-of-drug-induced-liver-injury-in-the-rat
#9
Petra Thulin, Robert J Hornby, Mariona Auli, Gunnar Nordahl, Daniel J Antoine, Philip Starkey Lewis, Christopher E Goldring, B Kevin Park, Neus Prats, Björn Glinghammar, Ina Schuppe-Koistinen
CONTEXT: There is an ongoing search for specific and translational biomarkers of drug-induced liver injury (DILI). MicroRNA-122 (miR-122) has previously shown potential as a sensitive, specific, and translational biomarker of DILI in both rodent, and human studies. OBJECTIVE: To build on previous work within the field, we examined biomarker kinetics in a rat model of acetaminophen (APAP)-induced liver injury to confirm the sensitivity, and specificity of miR-122 and glutamate dehydrogenase (GLDH)...
December 15, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/27966196/micrornas-33-122-and-208-a-potential-novel-targets-in-the-treatment-of-obesity-diabetes-and-heart-related-diseases
#10
REVIEW
Osama Abo Alrob, Said Khatib, Saleh A Naser
Despite decades of research, obesity and diabetes remain major health problems in the USA and worldwide. Among the many complications associated with diabetes is an increased risk of cardiovascular diseases, including myocardial infarction and heart failure. Recently, microRNAs have emerged as important players in heart disease and energy regulation. However, little work has investigated the role of microRNAs in cardiac energy regulation. Both human and animal studies have reported a significant increase in circulating free fatty acids and triacylglycerol, increased cardiac reliance on fatty acid oxidation, and subsequent decrease in glucose oxidation which all contributes to insulin resistance and lipotoxicity seen in obesity and diabetes...
December 14, 2016: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/27960338/photoclickable-microrna-for-the-intracellular-target-identification-of-micrornas
#11
Jinbo Li, Lei Huang, Xiao Xiao, Yingjie Chen, Xingxing Wang, Zhengquan Zhou, Chenyu Zhang, Yan Zhang
MicroRNAs (miRNAs) are important gene regulators that bind with target genes and repress target gene expression at the post-transcriptional level. The identification of target genes associated with miRNAs inside different cells is a major challenge in miRNA chemical biology due to the lack of functional miRNAs bearing appropriate tags. Here we report photoclickable miRNAs as appropriately pretagged miRNAs that keep the intracellular function of miRNAs and allow the addition of molecular handles through photoclick reaction...
December 14, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27956809/disease-specific-mir-34a-as-diagnostic-marker-of-non-alcoholic-steatohepatitis-in-a-chinese-population
#12
Xiao-Lin Liu, Qin Pan, Rui-Nan Zhang, Feng Shen, Shi-Yan Yan, Chao Sun, Zheng-Jie Xu, Yuan-Wen Chen, Jian-Gao Fan
AIM: To assess disease-specific circulating microRNAs (miRNAs) in non-alcoholic steatohepatitis (NASH) patients. METHODS: A total of 111 biopsy-proven non-alcoholic fatty liver disease (NAFLD) or chronic hepatitis B (CHB) patients and healthy controls from mainland China were enrolled to measure their serum levels of miR-122, -125b, -146b, -16, -21, -192, -27b and -34a. The correlations between serum miRNAs and histological features of NAFLD were determined. The diagnostic value of miRNA in NASH and significant fibrosis was analyzed and compared with that of cytokeratin-18 (CK-18), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI), respectively...
November 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27955628/analysis-of-association-between-circulating-mir-122-and-histopathological-features-of-nonalcoholic-fatty-liver-disease-in-patients-free-of-hepatocellular-carcinoma
#13
Norio Akuta, Yusuke Kawamura, Fumitaka Suzuki, Satoshi Saitoh, Yasuji Arase, Shunichiro Fujiyama, Hitomi Sezaki, Tetsuya Hosaka, Masahiro Kobayashi, Yoshiyuki Suzuki, Mariko Kobayashi, Kenji Ikeda, Hiromitsu Kumada
BACKGROUND: The association between circulating microRNA-122 (miR-122) and histopathological features of nonalcoholic fatty liver disease (NAFLD) remains unclear. METHODS: The association of serum miR-122 levels with histopathological features of NAFLD (steatosis, ballooning, lobular inflammation, and stage, as histological components of nonalcoholic steatohepatitis) was examined in serial liver biopsies from 36 hepatocellular carcinoma (HCC)-free Japanese patients with histopathologically-proven NAFLD...
December 12, 2016: BMC Gastroenterology
https://www.readbyqxmd.com/read/27943426/il-22-induced-mir-122-5p-promotes-keratinocyte-proliferation-by-targeting-sprouty2
#14
Meng Jiang, Weiyuan Ma, Yumei Gao, Kun Jia, Yan Zhang, Haidong Liu, Qing Sun
Psoriasis is a common inflammatory skin disease but the exact pathogenesis is largely unknown. Interleukin-22 (IL-22) has demonstrated its vital role in T cell-mediated immune response by interacting with keratinocytes in the pathogenesis of psoriasis. Here, we showed the differentially expressed miRNAs and their potential targets in HaCaT cells stimulated by IL-22 using miRNA and mRNA microarrays. We revealed a total of 20 significantly changed (more than 2-fold) miRNAs in HaCaT cells and validated the results with quantitative reverse transcriptase PCR (qRT-PCR)...
December 11, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27940300/molecular-regulation-of-lhcgr-expression-by-mir-122-during-follicle-growth-in-the-rat-ovary
#15
Bindu Menon, Thippeswamy Gulappa, K M J Menon
We have previously reported that LHCGR expression in the ovary is regulated through a post-transcriptional mechanism involving an mRNA binding protein designated as LRBP, which is regulated, at least in part, by a non-coding RNA, miR-122. Our present study examined the regulatory role of miR-122 in FSH-induced LHCGR expression during follicle development. Treatment of rat granulosa cells concurrently with FSH and 17β estradiol showed, as expected, a time-dependent increase in LHCGR mRNA levels as well as hCG-induced progesterone production...
December 8, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27917915/blood-hsa-mir-122-5p-and-hsa-mir-885-5p-levels-associate-with-fatty-liver-and-related-lipoprotein-metabolism-the-young-finns-study
#16
Emma Raitoharju, Ilkka Seppälä, Leo-Pekka Lyytikäinen, Jorma Viikari, Mika Ala-Korpela, Pasi Soininen, Antti J Kangas, Melanie Waldenberger, Norman Klopp, Thomas Illig, Jaana Leiviskä, Britt-Marie Loo, Niku Oksala, Mika Kähönen, Nina Hutri-Kähönen, Reijo Laaksonen, Olli Raitakari, Terho Lehtimäki
MicroRNAs are involved in disease development and may be utilized as biomarkers. We investigated the association of blood miRNA levels and a) fatty liver (FL), b) lipoprotein and lipid pathways involved in liver lipid accumulation and c) levels of predicted mRNA targets in general population based cohort. Blood microRNA profiling (TaqMan OpenArray), genome-wide gene expression arrays and nuclear magnetic resonance metabolomics were performed for Young Finns Study participants aged 34-49 years (n = 871)...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899485/circulating-microrna-122-is-associated-with-the-risk-of-new-onset-metabolic-syndrome-and-type-2-diabetes
#17
Peter Willeit, Philipp Skroblin, Alexander R Moschen, Xiaoke Yin, Dorothee Kaudewitz, Anna Zampetaki, Temo Barwari, Meredith Whitehead, Cristina M Ramírez, Leigh Goedeke, Noemi Rotllan, Enzo Bonora, Alun D Hughes, Peter Santer, Carlos Fernández-Hernando, Herbert Tilg, Johann Willeit, Stefan Kiechl, Manuel Mayr
MicroRNA-122 (miR-122) is abundant in the liver and involved in lipid homeostasis, but its relevance to the long-term risk of developing metabolic disorders is unknown. We therefore measured circulating miR-122 in the prospective population-based Bruneck Study (n=810; survey year: 1995). Circulating miR-122 was associated with prevalent insulin resistance, obesity, metabolic syndrome, type-2 diabetes, and an adverse lipid profile. Among 92 plasma proteins and 135 lipid subspecies quantified with mass spectrometry, it correlated inversely with zinc-alpha-2-glycoprotein and positively with afamin, complement-factor H, VLDL-associated apolipoproteins, and lipid subspecies containing monounsaturated and saturated fatty acids...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27895094/crosstalk-between-microrna-122-and-fox-family-genes-in-hepg2-cells
#18
Subodh Kumar, Ankita Batra, Shruthi Kanthaje, Sujata Ghosh, Anuradha Chakraborti
MicroRNA-122 (miR-122) is liver specific and plays an important role in physiology as well as diseases including hepatocellular carcinoma (HCC). Downregulation of miR-122 in HCC modulates apoptosis. Similarly, the putative targets of miR-122, the forkhead box (FOX) family genes also play an important role in the regulation of apoptosis. Hence, an interplay between miR-122 and FOX family genes has been explored in this study. Initially, an augmentation of apoptosis was noticed in HepG2 cells after transfection with miR-122...
November 28, 2016: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27883021/identification-of-aberrant-trna-halves-expression-patterns-in-clear-cell-renal-cell-carcinoma
#19
Malin Nientiedt, Mario Deng, Doris Schmidt, Sven Perner, Stefan C Müller, Jörg Ellinger
Small non-coding RNAs (sncRNA; <200 nt) regulate various cellular processes and modify gene expression. Under nutritional, biological or physiochemical stress some mature sncRNAs (e.g. tRNAs) are cleaved into halves (30-50 nt) and smaller fragments (18-22 nt); the significance and functional role of these tRNA fragments is unknown, but their existence has been linked to carcinogenesis. We used small RNA sequencing to determine the expression of sncRNAs. Subsequently the findings were validated for miR-122-5p, miR-142-3p and 5'tRNA4-Val-AAC using qPCR...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27879410/triple-staining-including-foxa2-identifies-stem-cell-lineages-undergoing-hepatic-and-biliary-differentiation-in-cirrhotic-human-liver
#20
Charles E Rogler, Remon Bebawee, Joe Matarlo, Joseph Locker, Nicole Pattamanuch, Sanjeev Gupta, Leslie E Rogler
Recent investigations have reported many markers associated with human liver stem/progenitor cells, "oval cells," and identified "niches" in diseased livers where stem cells occur. However, there has remained a need to identify entire lineages of stem cells as they differentiate into bile ducts or hepatocytes. We have used combined immunohistochemical staining for a marker of hepatic commitment and specification (FOXA2 [Forkhead box A2]), hepatocyte maturation (Albumin and HepPar1), and features of bile ducts (CK19 [cytokeratin 19]) to identify lineages of stem cells differentiating toward the hepatocytic or bile ductular compartments of end-stage cirrhotic human liver...
January 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
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