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Integration of high?throughput data of microRNA and mRNA expression profiles reveals novel insights into the mechanism of liver fibrosis.

ABSTRACT: Numerous studies have revealed that microRNAs (miRNAs) are functional non?coding RNAs that serve roles in a variety of biological processes. However, the expression patterns and regulatory networks, as well as the miRNAs involved in liver fibrosis remain to be elucidated. In the present study, a mouse model of liver fibrosis was constructed by CCl4 intraperitoneal injection and the total RNAs were extracted from the liver of the mice. The total RNAs were then sequenced on an Illumina HiSeq 2000 platform and an integrated analysis of miRNA and mRNA expression profiles in CCl4?induced liver fibrosis was performed. Compared with normal liver samples, 56 and 15 miRNAs were found to be upregulated and downregulated in fibrotic livers, respectively. To predict the potential functions of these miRNAs, bioinformatics analysis, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, was used to assess target mRNAs. The results indicated that the mitogen?activated protein kinase, phosphoinositide 3 kinase/protein kinase B and focal adhesion signaling pathways were the most significantly enriched. In addition, a regulatory network containing five dysregulated miRNAs and 22 target mRNAs was constructed based on their inverse correlation. Furthermore, the five dysregulated miRNAs were significantly upregulated and the expression of RELB, RAP1A, PPP3CB, MAP2K4, ARRB1, MAP3K4, FGF1 and PRKCB in the network was significantly decreased in LX?2 cells following TGF??1 treatment which suggested that they were associated with the activation of human hepatic stellate cells. The miRNA?mRNA regulatory network produced in the present study may provide novel insights into the role of miRNAs in liver fibrosis.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6297784 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Integration of high‑throughput data of microRNA and mRNA expression profiles reveals novel insights into the mechanism of liver fibrosis.

Zhang Yitong Y Liu Jing J Ma Yanyun Y Wang Jingjie J Zhu Jie J Liu Jie J Zhang Jun J

Molecular medicine reports 20181109 1

Numerous studies have revealed that microRNAs (miRNAs) are functional non‑coding RNAs that serve roles in a variety of biological processes. However, the expression patterns and regulatory networks, as well as the miRNAs involved in liver fibrosis remain to be elucidated. In the present study, a mouse model of liver fibrosis was constructed by CCl4 intraperitoneal injection and the total RNAs were extracted from the liver of the mice. The total RNAs were then sequenced on an Illumina HiSeq 2000 ...[more]

PMID: 30431126

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Project description:OBJECTIVES:Renal transplantation is the preferred method for most patients with end-stage renal disease, however, acute renal allograft rejection is still a major risk factor for recipients leading to renal injury. To improve the early diagnosis and treatment of acute rejection, study on the molecular mechanism of it is urgent. METHODS:MicroRNA (miRNA) expression profile and mRNA expression profile of acute renal allograft rejection and well-functioning allograft downloaded from ArrayExpress database were applied to identify differentially expressed (DE) miRNAs and DE mRNAs. DE miRNAs targets were predicted by combining five algorithm. By overlapping the DE mRNAs and DE miRNAs targets, common genes were obtained. Differentially co-expressed genes (DCGs) were identified by differential co-expression profile (DCp) and differential co-expression enrichment (DCe) methods in Differentially Co-expressed Genes and Links (DCGL) package. Then, co-expression network of DCGs and the cluster analysis were performed. Functional enrichment analysis for DCGs was undergone. RESULTS:A total of 1270 miRNA targets were predicted and 698 DE mRNAs were obtained. While overlapping miRNA targets and DE mRNAs, 59 common genes were gained. We obtained 103 DCGs and 5 transcription factors (TFs) based on regulatory impact factors (RIF), then built the regulation network of miRNA targets and DE mRNAs. By clustering the co-expression network, 5 modules were obtained. Thereinto, module 1 had the highest degree and module 2 showed the most number of DCGs and common genes. TF CEBPB and several common genes, such as RXRA, BASP1 and AKAP10, were mapped on the co-expression network. C1R showed the highest degree in the network. These genes might be associated with human acute renal allograft rejection. CONCLUSIONS:We conducted biological analysis on integration of DE mRNA and DE miRNA in acute renal allograft rejection, displayed gene expression patterns and screened out genes and TFs that may be related to acute renal allograft rejection.

Project description:BackgroundAccumulating evidences demonstrated that microRNA-target gene pairs were closely related to tumorigenesis and development. However, the correlation between miRNA and target gene was insufficiently understood, especially its changes between tumor and normal tissues.ObjectivesThe aim of this study was to evaluate the changes of correlation of miRNAs-target pairs between normal and tumor.Materials and methods5680 mRNA and 5740 miRNA expression profiles of 11 major human cancers were downloaded from the Cancer Genome Atlas (TCGA). The 11 cancer types were bladder urothelial carcinoma, breast invasive carcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, and thyroid carcinoma. For each cancer type, we firstly obtained differentially expressed miRNAs (DEMs) and genes (DEGs) in tumor and then acquired critical miRNA-target gene pairs by combining DEMs, DEGs and two experimentally validated miRNA-target interaction databases, miRTarBase and miRecords. We collected samples with both miRNA and mRNA expression values and performed a correlation analysis by Pearson method for miRNA-target pairs in normal and tumor, respectively.ResultsWe totally got 4743 critical miRNA-target pairs across 11 cancer types, and 4572 of them showed weaker correlation in tumor than in normal. The average correlation coefficients of miRNA-target pairs were different greatly between normal (-0.38 ~ -0.61) and tumor (-0.04 ~ -0.26) for 11 cancer type. The pan-cancer network, which consisted of 108 edges connecting 35 miRNAs and 89 target genes, showed the interactions of pairs appeared in multicancers.ConclusionsThis comprehensive analysis revealed that correlation between miRNAs and target genes was greatly reduced in tumor and these critical pairs we got were involved in cellular adhesion, proliferation, and migration. Our research could provide opportunities for investigating cancer molecular regulatory mechanism and seeking therapeutic targets.

Project description:To identify the regulatory network of known and novel microRNAs (miRNAs) and their targets responding to salt stress, a combined analysis of mRNA libraries, small RNA libraries, and degradome libraries were performed. In this study, we used unique molecular identifiers (UMIs), which are more sensitive, accurate, and reproducible than traditional methods of sequencing, to quantify the number of molecules and correct for amplification bias. We identified a total of 312 cotton miRNAs using seedlings at 0, 1, 3, and 6 h after NaCl treatment, including 80 known ghr-miRNAs and 232 novel miRNAs and found 155 miRNAs that displayed significant differential expression under salt stress. Among them, fifty-nine differentially expressed miRNAs were simultaneously induced in two or three tissues, while 66, 11, and 19 were specifically expressed in the roots, leaves, and stems, respectively. It is indicated there were different populations of miRNAs against salt stress in roots, leaves and stems. 399 candidate targets of salt-induced miRNAs showed significant differential expression before and after salt treatment, and 72 targets of 25 miRNAs were verified by degradome sequencing data. Furthermore, the regulatory relationship of miRNA-target gene was validated experimentally via 5'RLM-RACE, proving our data reliability. Gene ontology and KEGG pathway analysis found that salt-responsive miRNA targets among the differentially expressed genes were significantly enriched, and mainly involved in response to the stimulus process and the plant hormone signal transduction pathway. Furthermore, the expression levels of newly identified miRNA mir1 and known miRNAs miR390 and miR393 gradually decreased when subjected to continuous salt stress, while overexpression of these miRNAs both increased sensitivity to salt stress. Those newly identified miRNAs and mRNA pairs were conducive to genetic engineering and better understanding the mechanisms responding to salt stress in cotton.

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Integration of high?throughput data of microRNA and mRNA expression profiles reveals novel insights into the mechanism of liver fibrosis.

Publications

Integration of high‑throughput data of microRNA and mRNA expression profiles reveals novel insights into the mechanism of liver fibrosis.

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