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Kevin Appourchaux, Safi Dokmak, Matthieu Resche-Rigon, Xavier Treton, Martine Lapalus, Charles-Henry Gattolliat, Emmanuelle Porchet, Michelle Martinot-Peignoux, Nathalie Boyer, Michel Vidaud, Pierre Bedossa, Patrick Marcellin, Ivan Bièche, Emilie Estrabaud, Tarik Asselah
Staging fibrosis is crucial for the prognosis and to determine the rapid need of treatment in patients with chronic hepatitis B (CHB) and C (CHC). The expression of 13 fibrosis-related microRNAs (miRNAs) (miR-20a, miR-21, miR-27a, miR-27b, miR-29a, miR-29c, miR-92a, miR-122, miR-146a, miR-155, miR-221, miR-222, and miR-224) was analyzed in 194 serums and 177 liver biopsies of patients with either CHB or CHC to develop models to diagnose advanced fibrosis and cirrhosis (Metavir F3-F4). In CHB patients, the model (serum miR-122, serum miR-222, platelet count and alkaline phosphatase) was more accurate than APRI and FIB-4 to discriminate in between mild and moderate fibrosis (F1-F2) and F3-F4 (AUC of CHB model: 0...
October 12, 2016: Scientific Reports
Xiao Xiao, Jing Hu, Xingxing Wang, Lei Huang, Yingjie Chen, Wei Wang, Jinbo Li, Yan Zhang
A supramolecular hydrogel formed by spiropyran conjugated galactose was developed for light-controlled release of miR-122 and target-mediated delivery of the miRNA into HepG2 cells cultured on top of the gel.
October 13, 2016: Chemical Communications: Chem Comm
Donald B Smith, Paul Becher, Jens Bukh, Ernest A Gould, Gregor Meyers, Thomas Monath, A Scott Muerhoff, Alexander Pletnev, Rebecca Rico-Hesse, Jack T Stapleton, Peter Simmonds
Proposals are described for the assignment of recently reported viruses, infecting rodents, bats and other mammalian species, to new species within the Hepacivirus and Pegivirus genera (Family Flaviviridae). Assignments into 14 Hepacivirus species (Hepacivirus A to N) and 11 Pegivirus species (Pegivirus A to K) are based on phylogenetic relationships and sequence distances between conserved regions extracted from complete coding sequences of each proposed taxon. We propose that the species hepatitis C virus is renamed Hepacivirus C in order to acknowledge its unique historical position and so as to minimise confusion...
September 28, 2016: Journal of General Virology
Zeinab Ahsani, Samira Mohammadi-Yeganeh, Vahid Kia, Hamzeh Karimkhanloo, Nosratollah Zarghami, Mahdi Paryan
Hepatocellular carcinoma (HCC) is an invasive form of hepatic cancer arising from the accumulation of multiple genetic alterations. In this study, the causal role of disturbed canonical Wnt/β-catenin pathway was approved, and some of HCC-driven important gene candidates were determined. MicroRNAs (miRNAs), small non-coding RNAs, are the key regulators of important cancer genes, and their participation in tumorigenesis has been shown. By reviewing literature, WNT1 gene with functional significance was selected to approve miRNAs as new subjects for targeted therapy...
September 29, 2016: Applied Biochemistry and Biotechnology
Feng Pan, Jinwei You, Yuan Liu, Xuefeng Qiu, Wen Yu, Jiehua Ma, Lianjun Pan, Aixia Zhang, Qipeng Zhang
To better understand the molecular aetiology of type 2 diabetes mellitus-associated erectile dysfunction (T2DMED) and to provide candidates for further study of its diagnosis and treatment, this study was designed to investigate differentially expressed microRNAs (miRNAs) in the corpus cavernosum (CC) of mice with T2DMED using GeneChip array techniques (Affymetrix miRNA 4.0 Array) and to predict target genes and signalling pathways regulated by these miRNAs based on bioinformatic analysis using TargetScan, the DAIAN web platform and DAVID...
September 28, 2016: Molecular Genetics and Genomics: MGG
Xi Jin, Chun-Yan Feng, Zun Xiang, Yi-Peng Chen, You-Ming Li
The pathogenesis of nonalcoholic steatohepatitis (NASH) is still unclear, where involvement of circRNA is considered for its active role as "miRNA sponge". Therefore, we aimed to investigate the circRNA expression pattern in NASH and further construct the circRNA-miRNA-mRNA network for in-depth mechanism exploration. Briefly, NASH mice model was established by Methionine and choline deficiency (MCD) diet feeding. Liver circRNA and mRNA profile was initially screened by microarray and ensuing qRT-PCR verification was carried out...
September 22, 2016: Oncotarget
Gesche K Gerresheim, Nadia Dünnes, Anika Nieder-Röhrmann, Lyudmila A Shalamova, Markus Fricke, Ivo Hofacker, Christian Höner Zu Siederdissen, Manja Marz, Michael Niepmann
We have analyzed the binding of the liver-specific microRNA-122 (miR-122) to three conserved target sites of hepatitis C virus (HCV) RNA, two in the non-structural protein 5B (NS5B) coding region and one in the 3' untranslated region (3'UTR). miR-122 binding efficiency strongly depends on target site accessibility under conditions when the range of flanking sequences available for the formation of local RNA secondary structures changes. Our results indicate that the particular sequence feature that contributes most to the correlation between target site accessibility and binding strength varies between different target sites...
September 27, 2016: Cellular and Molecular Life Sciences: CMLS
Yi-Hao Yen, Chao-Min Huang, Kuo-Liang Wei, Jing-Houng Wang, Sheng-Nan Lu, Chuan-Mo Lee, Chao-Hung Hung, Chien-Hung Chen, Po-Lin Tseng, Kuo-Chin Chang, Ming-Chao Tsai, Ming-Tsung Lin, Cheng-Kun Wu, Cheng-Hong Yang, Sin-Hua Moi, Chung-Lung Cho, Tsung-Hui Hu
It has been demonstrated that microRNA-122 (miR-122) plays key roles in the modulation of hepatitis B virus (HBV) replication. This study examined the role of miR-122 in patients with hepatitis C virus (HCV)-HBV dual infection with active hepatitis C who received pegylated interferon-α and ribavirin dual therapy. We enrolled 121 patients with HCV-HBV dual infection after dual therapy. Stored serum was collected before treatment. RT-PCR was used to analyze miR-122. HBsAg seroclearance was noted in 37 (30.1%) cases during a median follow-up period of 5...
September 26, 2016: Scientific Reports
Laura Rivoli, A D Bastiaan Vliegenthart, Carmelita M J de Potter, Job J M H van Bragt, Nikolaos Tzoumas, Peter Gallacher, Tariq E Farrah, Neeraj Dhaun, James W Dear
AIM: microRNA-122 (miR-122) is a hepatotoxicity biomarker with utility in the management of paracetamol overdose and in drug development. Renal dysfunction and haemodialysis have been associated with a reduction in circulating microRNA. The objective of this study was to determine their effect on miR-122. METHODS: Blood samples were collected from 17 patients with end-stage renal disease (ESRD) on haemodialysis, 22 healthy controls, 30 patients with chronic kidney disease (CKD) and 15 patients post-kidney transplantation...
September 21, 2016: British Journal of Clinical Pharmacology
Wei Wang, Wen Bin Liu, Da Bing Huang, Wei Jia, Chu Shu Ji, Bing Hu
Drug resistance is one of the main hurdles for the successful treatment of hepatic carcinoma. However, the detailed mechanisms underlying resistance remain largely unknown and therapeutic approaches are limited. In the present study, we show that miR-122 confers resistance to 5-fluorouracil induced hepatocellular carcinoma cell apoptosis in vitro and reduces the potency of 5-fluorouracil in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicate that miR-122 modulates drug resistance through down-regulation of expression of PCDH20, which belongs to the protocadherin gene family and negatively regulates Akt activation...
2016: American Journal of Cancer Research
S Khanizadeh, M Ravanshad, S Y Hosseini, P Davoodian, A N Zadeh, F Sabahi, J Sarvari, Z Khanlari, M Hasani-Azad
The various roles of hepatitis C virus (HCV) NS3 protein in viral pathogenesis are emphasized, especially in the progression of fibrosis and tumors. The levels of miR-122 have been widely accepted as a critical factor in viral pathogenesis and disease progression. However, the possible correlation between miR-122 levels and fibrosis state has been less investigated. Therefore, in this study, plasmids expressing protease competent and protease mutated non-structural proteins 3 (NS3) were transfected into LX-2 cell line...
2016: Acta Virologica
Junxia Cui, Qing Chu, Tianjun Xu
Innate and acquired immune responses provide critical line in defense against pathogens. MicroRNAs (miRNAs) play crucial roles in regulate gene expression in inflammation and innate immunity. However, the main role of miRNAs are in a large part unclear in aquatic organisms. In this study, we found that miR-122 displayed dramatically declined expression profiles in Vibrio anguillarum challenged miiuy croaker. Meanwhile, we have explored TLR14 as a novel target gene of miR-122 involved in miiuy croakers inflammatory and immune response, which were further estimated through negative expression profiles in both Vibrio anguillarum challenged miiuy croaker and LPS exposure macrophages...
September 13, 2016: Fish & Shellfish Immunology
Melanie Maierthaler, Axel Benner, Michael Hoffmeister, Harald Surowy, Lina Jansen, Phillip Knebel, Jenny Chang-Claude, Hermann Brenner, Barbara Burwinkel
Circulating microRNAs (miRNAs) have been proposed as minimally invasive prognostic markers for various types of cancers, including colorectal cancer (CRC), the third most diagnosed cancer worldwide. We aimed to evaluate the levels of circulating miRNAs that might serve as markers for CRC prognosis and survival. We included plasma samples of 543 CRC patients with stage I-IV disease from a population-based study carried out in Germany. After comprehensive evaluation of current literature, 95 miRNAs were selected and measured with Custom TaqMan® Array MicroRNA Cards...
September 15, 2016: International Journal of Cancer. Journal International du Cancer
Jing Dong, Ying-Zhi Liang, Jie Zhang, Li-Juan Wu, Shuo Wang, Qi Hua, Yu-Xiang Yan
AIM: To explore the relationship between lipometabolism-related microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) and the presence of coronary artery disease (CAD). METHODS: In the present study, 161 stable CAD patients and 149 health controls were enrolled. The expression levels of seven miRNAs (miR-21, miR-24, miR-29a, miR-33a, miR-34a, miR-103a, and miR-122) in PBMCs were qualified by quantitative real-time polymerase chain reaction (qRT-PCR). The miRNA markers that showed significant difference between the two groups were used for further analysis...
September 13, 2016: Journal of Atherosclerosis and Thrombosis
Elena Senís, Stefan Mockenhaupt, Daniel Rupp, Tobias Bauer, Nagarajan Paramasivam, Bettina Knapp, Jan Gronych, Stefanie Grosse, Marc P Windisch, Florian Schmidt, Fabian J Theis, Roland Eils, Peter Lichter, Matthias Schlesner, Ralf Bartenschlager, Dirk Grimm
Successful RNAi applications depend on strategies allowing robust and persistent expression of minimal gene silencing triggers without perturbing endogenous gene expression. Here, we propose a novel avenue which is integration of a promoterless shmiRNA, i.e. a shRNA embedded in a micro-RNA (miRNA) scaffold, into an engineered genomic miRNA locus. For proof-of-concept, we used TALE or CRISPR/Cas9 nucleases to site-specifically integrate an anti-hepatitis C virus (HCV) shmiRNA into the liver-specific miR-122/hcr locus in hepatoma cells, with the aim to obtain cellular clones that are genetically protected against HCV infection...
September 9, 2016: Nucleic Acids Research
Mercedes Robles-Díaz, Inmaculada Medina-Caliz, Camilla Stephens, Raúl J Andrade, M Isabel Lucena
Despite being relatively rare, drug-induced liver injury (DILI) is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings, and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make...
2016: Frontiers in Pharmacology
Nuno Cortez-Dias, Marina C Costa, Pedro Carrilho-Ferreira, Doroteia Silva, Cláudia Jorge, Carina Calisto, Teresa Pessoa, Susana Robalo Martins, João Carvalho de Sousa, Pedro Canas da Silva, Manuela Fiúza, António Nunes Diogo, Fausto J Pinto, Francisco J Enguita
BACKGROUND: MicroRNAs (miRNAs) are key players in cardiovascular development and disease. However, not only miRNAs of a cardiac origin have a critical role in heart function. Recent studies have demonstrated that miR-122-5p, a hepatic miRNA, increases in the bloodstream during ischemic cardiogenic shock and it is upregulated in the infarcted myocardium. The aim of the present study was to determine the potential of circulating miR-122-5p as a biomarker for early prognostic stratification of ST-segment elevation acute myocardial infarction (STEMI) patients...
September 23, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
Shengnan Wei, Ming Zhang, Yang Yu, Huan Xue, Xiaoxin Lan, Shuping Liu, Grant Hatch, Li Chen
Hepatocyte Nuclear Factor-4α (HNF-4α) is a key nuclear receptor protein required for liver development. miR-122 is a predominant microRNA expressed in liver and is involved in the regulation of cholesterol and fatty acid metabolism. HNF-4α is know to regulate expression of miR-122 in liver. We examined how HNF-4α regulated gluconeogenesis and lipid metabolism through miR-122 in vivo and in vitro. Expression of miR-122, HNF-4α, phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol response elementary binding protein-1 (SREBP-1), fatty acid synthase-1 (FAS-1), carnitine palmitoyltransferase-1 (CPT-1) and acetyl Coenzyme A carboxylase alpha (ACCα) were determined in livers of Type 2 diabetic mice and in insulin resistant palmitate-treated HepG2 cells...
August 31, 2016: European Journal of Pharmacology
Peter Sarnow, Selena M Sagan
Many viruses encode or subvert cellular microRNAs (miRNAs) to aid in their gene expression, amplification strategies, or pathogenic signatures. miRNAs typically downregulate gene expression by binding to the 3' untranslated region of their mRNA targets. As a result, target mRNAs are translationally repressed and subsequently deadenylated and degraded. Curiously, hepatitis C virus (HCV), a member of the Flaviviridae family, recruits two molecules of liver-specific microRNA-122 (miR-122) to the 5' end of its genome...
September 29, 2016: Annual Review of Virology
Wanqian Liang, Junxia Guo, Jianhua Li, Caiyan Bai, Yuan Dong
MicroRNA-122 has been reported to play a potential role in the apoptosis of myocardial cells. However, the effect of miR-122 in regulating myocardial ischemic injury has not been previously addressed. This study aimed to investigate the effect and the molecular basis of miR-122 on myocardial ischemic injury. Using the hypoxia/reoxygenation (H/R) model of rat cardiomyocytes H9C2 in vitro, we found that miR-122 was highly expressed in H9C2 cells after H/R treatment. Overexpression of miR-122 by recombinant adeno-associated viral vector infection markedly promoted the apoptosis of H9C2 cells induced by H/R treatment, whereas miR-122 inhibition significantly decreased cell apoptosis...
September 23, 2016: Biochemical and Biophysical Research Communications
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