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Integrative analysis of microRNA and mRNA expression profiles in fetal rat model with anorectal malformation.

ABSTRACT: Background:Anorectal malformations (ARMs) are the most common congenital malformation of the gut, and regulated by multiple signal transduction pathways. The microRNA (miRNA) expression profiles and their biologial functions in anorectal malformations (ARMs) remain unclear. The aim of our study was to evaluate miRNA and mRNA expression profiles in the ARM rats. Methods and Materials:ARM was induced with ethylenethiourea (ETU) on gestational day 10. Cesarean deliveries were performed to harvest the embryos on gestional day 20. For the extraction of total RNA, 1 cm terminal hindgut samples were obtained from three fetal rats that had similar weights. The microarrays and quantitative RT-PCR analysis were conducted to evaluate the miRNA and mRNA expression profiles in normal fetal rats (n = 3) and ARM fetal rats (n = 3). Results:In total, 33 miRNAs and 772 mRNAs were significantly and differentially expressed in terminal hindgut tissues of ARM group versus control group. Functional annotation was performed to understand the functions and pathways of differentially expressed mRNAs. Also, we constructed a miRNA-target gene regulatory network including 25 differentially expressed miRNAs and 76 mRNAs. Furthermore, the credibility of the microarray-based results were validated by using qRT-PCR. Conclusion:The miRNA and mRNA expression in terminal hindgut tissue of ARM fetal rats might provide a basis for further research on the pathogenesis of ARMs.

SUBMITTER: Xiao H

PROVIDER: S-EPMC6203938 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Integrative analysis of microRNA and mRNA expression profiles in fetal rat model with anorectal malformation.

Xiao Hui H Huang Rui R Diao Mei M Li Long L Cui XiaoDai X

PeerJ 20181024

<h4>Background</h4>Anorectal malformations (ARMs) are the most common congenital malformation of the gut, and regulated by multiple signal transduction pathways. The microRNA (miRNA) expression profiles and their biologial functions in anorectal malformations (ARMs) remain unclear. The aim of our study was to evaluate miRNA and mRNA expression profiles in the ARM rats.<h4>Methods and materials</h4>ARM was induced with ethylenethiourea (ETU) on gestational day 10. Cesarean deliveries were perform ...[more]

PMID: 30386697

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Project description:PurposeExposure to radiation provokes cellular responses, which are likely regulated by gene expression networks. MicroRNAs are small non-coding RNAs, which regulate gene expression by promoting mRNA degradation or inhibiting protein translation. The expression patterns of both mRNA and miRNA during the radiation-induced lung injury (RILI) remain less characterized and the role of miRNAs in the regulation of this process has not been studied. The present study sought to evaluate miRNA and mRNA expression profiles in the rat lung after irradiation.Methods and materialsMale Wistar rats were subjected to single dose irradiation with 20 Gy using 6 MV x-rays to the right lung. (A dose rate of 5 Gy/min was applied). Rats were sacrificed at 3, 12 and 26 weeks after irradiation, and morphological changes in the lung were examined by haematoxylin and eosin. The miRNA and mRNA expression profiles were evaluated by microarrays and followed by quantitative RT-PCR analysis.ResultsA cDNA microarray analysis found 2183 transcripts being up-regulated and 2917 transcripts down-regulated (P???0.05, ?2.0 fold change) in the lung tissues after irradiation. Likewise, a miRNAs microarray analysis indicated 15 miRNA species being up-regulated and 8 down-regulated (P???0.05). Subsequent bioinformatics analyses of the differentially expressed mRNA and miRNAs revealed that alterations in mRNA expression following irradiation were negatively correlated with miRNAs expression.ConclusionsOur results provide evidence indicating that irradiation induces alterations of mRNA and miRNA expression in rat lung and that there is a negative correlation of mRNA and miRNA expression levels after irradiation. These findings significantly advance our understanding of the regulatory mechanisms underlying the pathophysiology of radiation-induced lung injury. In summary, RILI does not develop gradually in a linear process. In fact, different cell types interact via cytokines in a very complex network. Furthermore, this study suggests that microRNAs may serve an important role in the pathogenesis of RILI and that understanding their role in RILI may have a significant effect on patient management and diagnosis in the future.

Project description:Transcription signatures have been used to stratify breast cancer patients into clinically distinct subgroups. However, transcription alone does not determine protein expression. Of potentially equal importance for determining the tumor phenotype is the rate at which transcripts are translated to form protein. Protein translation is controlled to a major degree by miRNA, and cancer cells may deregulate the expression of key genes by altering the activity of relevant miRNAs. The importance of miRNA deregulation and the extent to which multiple miRNAs coordinately deregulate key proteins in breast cancer is only partly understood. To gain such insight, we analyzed genome-wide miRNA expression and mRNA/protein expression for a panel of 105 selected cancer related genes in breast carcinomas from 283 patients. The miRNA-mRNA-protein interactome for the selected genes was constructed by modeling protein expression as a joint function of mRNA and miRNA expression, considering the effect of both one miRNA at a time, and all studied miRNAs simultaneously. The interactome represents a map of the global effects of miRNAs on protein expression, capturing direct as well as indirect effects. The results reveal extensive association between miRNA and protein expression as well as coordinated effects of multiple miRNAs on individual proteins. Applying the model onto two other independent primary breast cancer cohorts confirmed the generalizability of key aspects of the interactome map. The mRNA expression profiling of 283 breast cancer samples was performed using the SurePrint G3 Human GE 8x60K one-color microarrays from Agilent (Agilent Technologies, Santa Clara, CA, USA) according to the manufacturer’s protocol (One-Color Microarray-Based Gene Expression Analysis, Low Input Quick Amp Labeling, v.6.5, May 2010). For each sample, 100 ng of RNA was amplified and hybridized on the array. Scanning was performed with Agilent Scanner G2565A, using AgilentG3_GX_1Color as profile. Signals were extracted using FE v.10.7.3.1 and protocol GE1_107_Sep09 (Agilent Technologies). Arrays were log2-transformed, quantile normalized and hospital-adjusted by subtracting from each probe value the mean probe value among samples from the same hospital. The Oslo Breast Cancer Consortium (OSBREAC)

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Integrative analysis of microRNA and mRNA expression profiles in fetal rat model with anorectal malformation.

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Integrative analysis of microRNA and mRNA expression profiles in fetal rat model with anorectal malformation.

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