Abstract:
:MicroRNAs (miRNAs) crucial roles in translation repression and post-transcriptional adjustments contribute to regulate intestinal lipid metabolism. Even though their actions in different metabolic tissues have been elucidated, their intestinal activity is yet unclear. We aimed to investigate intestinal miRNA-regulated lipid metabolism-related genes, by creating an intestinal-specific Dicer1 knockout (Int-Dicer1 KO) mouse model, with a depletion of microRNAs in enterocytes. The levels of 83 cholesterol and lipoprotein metabolism-related genes were assessed in the intestinal mucosa of Int-Dicer1 KO and Wild Type C57BL/6 (WT) littermates mice at baseline and 2 h after an oral lipid challenge. Among the 18 genes selected for further validation, Hmgcs2, Acat1 and Olr1 were found to be strong candidates to be modulated by miRNAs in enterocytes and intestinal organoids. Moreover, we report that intestinal miRNAs contribute to the regulation of intestinal epithelial differentiation. Twenty-nine common miRNAs found in the intestines were analyzed for their potential to target any of the three candidate genes found and validated by miRNA-transfection assays in Caco-2 cells. MiR-31-5p, miR-99b-5p, miR-200a-5p, miR-200b-5p and miR-425-5p are major regulators of these lipid metabolism-related genes. Our data provide new evidence on the potential of intestinal miRNAs as therapeutic targets in lipid metabolism-associated pathologies.
journal_name
Front Genetjournal_title
Frontiers in geneticsauthors
Ruiz-Roso MB,Gil-Zamorano J,López de Las Hazas MC,Tomé-Carneiro J,Crespo MC,Latasa MJ,Briand O,Sánchez-López D,Ortiz AI,Visioli F,Martínez JA,Dávalos Adoi
10.3389/fgene.2020.00707subject
Has Abstractpub_date
2020-07-10 00:00:00pages
707issn
1664-8021journal_volume
11pub_type
杂志文章abstract::Growing evidences have indicated that microRNAs (miRNAs) play a significant role relating to many important bioprocesses; their mutations and disorders will cause the occurrence of various complex diseases. The prediction of miRNAs associated with underlying diseases via computational approaches is beneficial to ident...
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abstract::Cell viability and gene expression profiles are altered in cellular models of neurodegenerative disorders such as Huntington's Disease (HD). Using the yeast model system, we show that the SUMO-targeted ubiquitin ligase (STUbL) Slx5 reduces the toxicity and abnormal transcriptional activity associated with a mutant, ag...
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abstract::Periconceptional folic acid use can often prevent neural tube defects (NTDs). Variants of genes involved in folate metabolism in mothers and children have been associated with occurrence of NTDs. We identified Irish families with individuals affected by neural tube defects. In these families, we observed that neural t...
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abstract::Objective: Schizophrenia is thought to be a neurodevelopmental disorder. As a key regulator in the development of the central nervous system, transcription factor 4 (TCF4) has been shown to be involved in the pathogenesis of schizophrenia. The aim of our study was to assay the association of TCF4 single nucleotide pol...
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abstract::Background: Milroy disease (MD) is rare and autosomal dominant resulting from mutations of the vascular endothelial growth factor receptor-3 (VEGFR-3 or FLT4), which leads to dysgenesis of the lymphatic system. Methods: Here we report a Chinese MD family with 2 affected members of two generations. We identified the mu...
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abstract:Background:SOX2 overlapping transcript (SOX2-OT) produces alternatively spliced long non-coding RNAs (lncRNA). Previous studies of the prognostic role of SOX2-OT expression met with conflicting results. The aim of this study was to properly consider the prognostic role of SOX2-OT expression in several cancers. In addit...
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pub_type: 杂志文章,评审
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abstract::Autosomal dwarfism (adw) in chickens is a growth deficiency caused by a recessive mutation. Characteristic for adw is an approximately 30% growth reduction with short shank. The adw variant was first recognized in the Cornell K-strain of White Leghorns, but the genetic causal variant remained unknown. To identify the ...
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abstract::Since the turn of the century, researchers have sought to diagnose cancer based on gene expression signatures measured from the blood or biopsy as biomarkers. This task, known as classification, is typically solved using a suite of algorithms that learn a mathematical rule capable of discriminating one group ("cases")...
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abstract::Accurate inference of causal gene regulatory networks from gene expression data is an open bioinformatics challenge. Gene interactions are dynamical processes and consequently we can expect that the effect of any regulation action occurs after a certain temporal lag. However such lag is unknown a priori and temporal a...
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abstract:Background:Genetic association studies have identified single nucleotide polymorphisms (SNPs) related to chronic obstructive pulmonary disease (COPD) susceptibility. The aim of this study was to identify HHIP genetic variants associated with COPD, pulmonary function, and serum and sputum HHIP protein levels in Mexican ...
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abstract::RNA-binding proteins (RBPs) are a kind of gene regulatory factor that presents a significant biological effect in the initiation and development of various tumors, including bladder cancer (BLCA). However, the RBP-based prognosis signature for BLCA has not been investigated. In this study, we attempted to develop an R...
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doi:10.3389/fgene.2020.00992
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pub_type: 杂志文章,评审
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