scholarly journals Identification of key miRNAs in the progression of hepatocellular carcinoma using an integrated bioinformatics approach

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9000
Author(s):  
Qi Zheng ◽  
Xiaoyong Wei ◽  
Jun Rao ◽  
Cuncai Zhou

Backgroud It has been shown that aberrant expression of microRNAs (miRNAs) and transcriptional factors (TFs) is tightly associated with the development of HCC. Therefore, in order to further understand the pathogenesis of HCC, it is necessary to systematically study the relationship between the expression of miRNAs, TF and genes. In this study, we aim to identify the potential transcriptomic markers of HCC through analyzing common microarray datasets, and further establish the differential co-expression network of miRNAs–TF–mRNA to screen for key miRNAs as candidate diagnostic markers for HCC. Method We first downloaded the mRNA and miRNA expression profiles of liver cancer from the GEO database. After pretreatment, we used a linear model to screen for differentially expressed genes (DEGs) and miRNAs. Further, we used weighed gene co-expression network analysis (WGCNA) to construct the differential gene co-expression network for these DEGs. Next, we identified mRNA modules significantly related to tumorigenesis in this network, and evaluated the relationship between mRNAs and TFs by TFBtools. Finally, the key miRNA was screened out in the mRNA–TF–miRNA ternary network constructed based on the target TF of differentially expressed miRNAs, and was further verified with external data set. Results A total of 465 DEGs and 215 differentially expressed miRNAs were identified through differential genes expression analysis, and WGCNA was used to establish a co-expression network of DEGs. One module that closely related to tumorigenesis was obtained, including 33 genes. Next, a ternary network was constructed by selecting 256 pairs of mRNA–TF pairs and 100 pairs of miRNA–TF pairs. Network mining revealed that there were significant interactions between 18 mRNAs and 25 miRNAs. Finally, we used another independent data set to verify that miRNA hsa-mir-106b and hsa-mir-195 are good classifiers of HCC and might play key roles in the progression of HCC. Conclusion Our data indicated that two miRNAs—hsa-mir-106b and hsa-mir-195—are identified as good classifiers of HCC.

2019 ◽  
Vol 31 (4) ◽  
pp. 645 ◽  
Author(s):  
Jihyun Kim ◽  
Jaewang Lee ◽  
Jin Hyun Jun

Recurrent implantation failure (RIF) is one of the main causes for the repeated failure of IVF, and the major reason for RIF is thought to be a miscommunication between the embryo and uterus. However, the exact mechanism underlying embryo–uterus cross-talk is not fully understood. The aim of the present study was to identify differentially expressed microRNAs (miRNAs) among blastocysts, non-outgrowth and outgrowth embryos in mice using microarray analysis. A bioinformatics analysis was performed to predict the potential mechanisms of implantation. The miRNA expression profiles differed significantly between non-outgrowth and outgrowth embryos. In all, 3163 miRNAs were detected in blastocysts and outgrowth embryos. Of these, 10 miRNA candidates (let-7b, miR-23a, miR-27a, miR-92a, miR-183, miR-200c, miR-291a, miR-425, miR-429 and miR-652) were identified as significant differentially expressed miRNAs of outgrowth embryos by in silico analysis. The expression of the miRNA candidates was markedly changed during preimplantation embryo development. In particular, let-7b-5p, miR-200c-3p and miR-23a-3p were significantly upregulated in outgrowth embryos compared with non-outgrowth blastocysts. Overall, differentially expressed miRNAs in outgrowth embryos compared with blastocysts and non-outgrowth embryos could be involved in embryo attachment, and interaction between the embryo proper and maternal endometrium during the implantation process.


2014 ◽  
Vol 170 (4) ◽  
pp. 583-591 ◽  
Author(s):  
David Velázquez-Fernández ◽  
Stefano Caramuta ◽  
Deniz M Özata ◽  
Ming Lu ◽  
Anders Höög ◽  
...  

BackgroundThe adrenocortical adenoma (ACA) entity includes aldosterone-producing adenoma (APA), cortisol-producing adenoma (CPA), and non-hyperfunctioning adenoma (NHFA) phenotypes. While gene mutations and mRNA expression profiles have been partly characterized, less is known about the alterations involving microRNA (miRNA) expression.AimTo characterize miRNA expression profile in relation to the subtypes of ACAs.Subjects and methodsmiRNA expression profiles were determined in 26 ACAs (nine APAs, ten CPAs, and seven NHFAs) and four adrenal references using microarray-based screening. Significance analysis of microarrays (SAM) was carried out to identify differentially expressed miRNAs between ACA and adrenal cortices or between tumor subtypes. Selected differentially expressed miRNAs were validated in an extended series of 43 ACAs and ten adrenal references by quantitative RT-PCR.ResultsAn hierarchical clustering revealed separate clusters for APAs and CPAs, while the NHFAs were found spread out within the APA/CPA clusters. When NHFA was excluded, the clustering analysis showed a better separation between APA and CPA. SAM analysis identified 40 over-expressed and three under-expressed miRNAs in the adenomas as compared with adrenal references. Fourteen miRNAs were common among the three ACA subtypes. Furthermore, we found specific miRNAs associated with different tumor phenotypes.ConclusionThe results suggest that miRNA expression profiles can distinguish different subtypes of ACA, which may contribute to a deeper understanding of ACA development and potential therapeutics.


2021 ◽  
Vol 23 (1) ◽  
pp. 105
Author(s):  
Matic Bošnjak ◽  
Željka Večerić-Haler ◽  
Emanuela Boštjančič ◽  
Nika Kojc

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises autoimmune disease entities that cause target organ damage due to relapsing-remitting small vessel necrotizing vasculitis, and which affects various vascular beds. The pathogenesis of AAV is incompletely understood, which translates to considerable disease- and treatment-related morbidity and mortality. Recent advances have implicated microRNAs (miRNAs) in AAV; however, their accurate characterization in renal tissue is lacking. The goal of this study was to identify the intrarenal miRNA expression profile in AAV relative to healthy, non-inflammatory and inflammatory controls to identify candidate-specific miRNAs. Formalin-fixed, paraffin-embedded renal biopsy tissue samples from 85 patients were obtained. Comprehensive miRNA expression profiles were performed using panels with 752 miRNAs and revealed 17 miRNA that differentiated AAV from both controls. Identified miRNAs were annotated to characterize their involvement in pathways and to define their targets. A considerable subset of differentially expressed miRNAs was related to macrophage and lymphocyte polarization and cytokines previously deemed important in AAV pathogenesis, lending credence to the obtained results. Interestingly, several members of the miR-30 family were detected. However, a validation study of these differentially expressed miRNAs in an independent, larger sample cohort is needed to establish their potential diagnostic utility.


2010 ◽  
Vol 53 (6) ◽  
pp. 734-736
Author(s):  
H. B. He ◽  
S. H. Zhao ◽  
X. Y. Li

Abstract. MicroRNAs (miRNAs) are a class of short, non-coding regulatory RNAs, which are approximately 22 nucleotides in length. Typically, miRNAs negatively regulate gene expression by binding with the 3' untranslated region (UTR) of its regulatory target mRNAs. MicroRNAs are known to play diverse roles in fundamental biological processes, such as proliferation, differentiation and apoptosis (Bartel 2004, 2009). It has been reported that miR-1, miR-133, miR-181 and miR-206 play important roles in skeletal muscle proliferation and hypertrophy (Callis et al. 2007, McCarthy -Esser 2007). We have detected porcine miRNA expression profiles during different stage of skeletal muscle development and a total of 140 miRNAs were differentially expressed (HUANG et al. 2008). In this study, we mapped five differentially expressed miRNAs (mir-29c, mir-103-1, mir-127, mir-193b and mir-218-1) using the radiation hybrid (IMpRH) panel (YERLE et al. 1998).


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Ni Li ◽  
Jiangfang Lian ◽  
Sheng Zhao ◽  
Dawei Zheng ◽  
Xi Yang ◽  
...  

This study compared microRNA (miRNA) expression profiles between rheumatic heart disease (RHD) patients and healthy controls to investigate their differential expression and help elucidate their mechanisms of action. Microarray analysis was used to measure miRNA expression, and a total of 133 miRNAs were shown to be significantly upregulated in RHD patients compared with controls, including miR-1183 and miR-1299. A total of 137 miRNAs, including miR-4423-3p and miR-218-1-3p, were significantly downregulated in RHD patients. Quantitative real-time-PCR confirmed microarray findings for miR-1183 and miR-1299 in both tissue and plasma. Bioinformatic predictions were also made of differentially expressed miRNAs as biomarkers in RHD by databases and GO/pathway analysis. Furthermore, we investigated miR-1183 and miR-1299 expression in RHD patients with secondary pulmonary hypertension (PAH). Our findings identified an important role for miR-1299 as a direct regulator of RHD, while the observed difference in expression of miR-1183 between RHD-PAH patients with high or low pulmonary artery pressure suggests that miR-1183 overexpression may reflect pulmonary artery remodeling. miR-1183 and miR-1299 appear to play distinct roles in RHD pathogenesis accompanied by secondary PAH and could be used as potential biological markers for disease development.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Udari Eshani Perera ◽  
Habtamu B. Derseh ◽  
Sasika N. V. Dewage ◽  
Andrew Stent ◽  
Rukmali Wijayarathna ◽  
...  

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibroproliferative disorder that has one of the poorest prognoses amongst interstitial lung diseases. Recently, the finding of aberrant expression levels of miRNAs in IPF patients has drawn significant attention to the involvement of these molecules in the pathogenesis of this disease. Clarification of the differential expression of miRNAs in health and disease may identify novel therapeutic strategies that can be employed in the future to combat IPF. This study evaluates the miRNA expression profiles in a sheep model for lung fibrosis and compares them to the miRNA profiles of both IPF patients and the mouse bleomycin model for pulmonary fibrosis. Pathway enrichment analyses were performed on differentially expressed miRNAs to illustrate which biological mechanisms were associated with lung fibrosis. Results We discovered 49 differentially expressed miRNAs in the sheep fibrosis model, in which 32 miRNAs were significantly down regulated, while 17 miRNAs were significantly upregulated due to bleomycin-induced lung injury. Moreover, the miRNA families miR-29, miR-26, miR-30, let-7, miR-21, miR-19, miR-17 and miR-199 were aberrantly expressed in both sheep and mouse models, with similar differential miRNAs expression observed in IPF cases. Importantly, 18 miRNAs were aberrantly expressed in both the sheep model and IPF patients, but not in mice. Conclusion Together with pathway enrichment analyses, these results show that the sheep model can potentially be used to characterize previously unrecognized biological pathways associated with lung fibrosis.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Yanhua Lei ◽  
Ping Guo ◽  
Xiuguo Li ◽  
Yuanyuan Zhang ◽  
Ting Du

Background.Vestibular schwannoma (VS) is benign, slow-growing brain tumor that negatively impacts patient quality of life, which may cause even death. This study aimed to explore key genes and microRNAs (miRNAs) associated with VS.Methods.The mRNA and miRNA expression profiles of VS downloaded from Gene Expression Omnibus (GEO) database were included in this study to perform an integrated analysis. The differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) were identified. Then, functional annotation and protein-protein interaction networks (PPI) of DEmRNAs were constructed. DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed.Results.A total of 2627 DEmRNAs (1194 upregulated and 1433 downregulated DEmRNAs) and 21 DEmiRNAs (12 upregulated and 9 downregulated DEmiRNAs) were identified. ISG15, TLE1, and XPC were three hub proteins of VS-specific PPI network. A total of 2970 DEmiRNAs-DEmRNAs pairs were obtained. Among which, hsa-miR-181a-5p, hsa-miR-106-5p, and hsa-miR-34a-5p were the top three DEmiRNAs that covered most DEmRNAs. The functional annotation of DEmiRNA-target DEmRNAs revealed that the DEmiRNA-target DEmRNAs were significantly enriched in cGMP-PKG signaling pathway, adrenergic signaling in cardiomyocytes, and pathways in cancer.Conclusion.The results of this present study may provide a comprehensive understanding for the roles of DEmRNAs and DEmiRNAs in the pathogenesis of VS and developing potential biomarkers of VS.


2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Maoxing Pan ◽  
Yuanjun Deng ◽  
Chuiyang Zheng ◽  
Huan Nie ◽  
Kairui Tang ◽  
...  

Objective. The purpose of present study was to investigate the potential mechanism underlying the protective effect of Shenling Baizhu San (SLBZS) on nonalcoholic fatty liver disease (NAFLD) by microRNA (miRNA) sequencing. Methods. Thirty male Wistar rats were randomly divided into a normal control (NC) group, a high-fat diet (HFD) group, and an SLBZS group. After 12 weeks, the biochemical parameters and liver histologies of the rats were assessed. The Illumina HiSeq 2500 sequencing platform was used to analyse the hepatic miRNA expression profiles. Representative differentially expressed miRNAs were further validated by qRT-PCR. The functions of the differentially expressed miRNAs were analysed by bioinformatics. Results. Our results identified 102 miRNAs that were differentially expressed in the HFD group compared with the NC group. Among those differentially expressed miRNAs, the expression levels of 28 miRNAs were reversed by SLBZS administration, suggesting the modulation effect of SLBZS on hepatic miRNA expression profiles. The qRT-PCR results confirmed that the expression levels of miR-155-5p, miR-146b-5p, miR-132-3p, and miR-34a-5p were consistent with those detected by sequencing. Bioinformatics analyses indicated that the target genes of the differentially expressed miRNAs reversed by SLBZS were mainly related to metabolic pathways. Conclusion. This study provides novel insights into the mechanism of SLBZS in protecting against NAFLD; this mechanism may be partly related to the modulation of hepatic miRNA expression and their target pathways.


2020 ◽  
Vol 15 ◽  
Author(s):  
Jianwei Li ◽  
Leibo Liu ◽  
Qinghua Cui ◽  
Yuan Zhou

Background: De-regulation of microRNAs (miRNAs) is closely related with many complex diseases including cancers. In The Cancer Genome Atlas (TCGA), hundreds of differentially expressed miRNAs are stored for each type of cancer, which are hard to be intuitively interpreted. To date, several miRNA set enrichment tools have been tailored to predict the potential disease associations and functions of de-regulated miRNAs, including the miRNA Enrichment Analysis and Annotation tool (miEAA) and Tool for Annotations of human MiRNAs (TAM 1.0 & TAM 2.0). However, independent benchmarking of these tools is warranted to assess their effectiveness and robustness, and the relationship between enrichment analysis results and the prognosis significance of cancers. Method: Base on differentially expressed miRNAs from expression profiles in TCGA, we performed a series of tests and comprehensive comparison of the enrichment analysis results of miEAA, TAM 1.0 and TAM 2.0. The work focused on the performance of the three tools, disease similarity based on miRNA-disease associations from the enrichment analysis results, the relationship between the overrepresented miRNAs from enrichment analysis results and the prognosis significance of cancers. Results: The main results show that TAM 2.0 is more likely to identify the regulatory disease’s functions of de-regulated miRNA; it is feasible to calculate disease similarity based on enrichment analysis results of TAM 2.0; and there is weak positive correlation between the occurrence frequency of miRNAs in the TAM 2.0 enrichment analysis results and the prognosis significance of the cancer miRNAs. Conclusion: Our comparison results not only provide a reference for biomedical researchers to choose appropriate miRNA set enrichment analysis tools to achieve their own purpose, but also demonstrate that the degree of overrepresentation of miRNAs could be a supplementary indicator of the disease similarity and the prognostic effect of cancer miRNAs.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 570-570
Author(s):  
Svenja Daschkey ◽  
Silja Röttgers ◽  
Jutta Bradtke ◽  
Andrea Teigler-Schlegel ◽  
Arndt Borkhardt ◽  
...  

Abstract Abstract 570 microRNAs (miRNAs) are small (21-24 nt), non-coding and highly conserved molecules, which are involved in several important regulatory processes like cell growth, proliferation, differentiation, immune response and apoptosis. Thus, their involvement in the pathogenesis of several diseases, including acute myeloid leukemia (AML) is not surprising. Several studies address the miRNA expression changes in adulthood AML, however, comprehensive studies in AML of children and adolescents are missing so far. We investigated the miRNA expression profiles of different AML subtypes from pediatric patients, in order to identify differentially expressed miRNAs. Subsequently, appropriate cell line models were used for global biochemical identification of miRNA targeting structures. miRNA expression profiles of 102 pediatric AML patient samples were identified using microarray technology, and analyzed by unsupervised hierarchical cluster analysis and statistical testing. AML subtypes with translocations t(8;21) and t(15;17) can be separated from each other, solely based on their miRNA expression profile, while other translocations involving mixed-lineage leukemia (MLL) rearrangements are interspersed and lack a characteristic miRNA signature. Only six and seven miRNAs are differentially expressed between AML samples with translocations t(8;21) and t(15;17), respectively, and all other AML subtypes. This is surprising, since patients of different AML subtypes, investigated in this study, differ greatly in their clinical presentation. Differentially expressed miRNAs contain lineage specific miRNAs (miR-223), oncogenic miRNAs (miR-21) and more ubiquitously expressed miRNAs (let-7b/c, miR-100, −125b and −181a/b) with no designated characteristics. Furthermore, these differentially expressed miRNAs were not described as abundant in adult AML patients. To gain further insights into the function of differentially expressed miRNAs, we established a modified PAR-CLIP method termed PAR-CLIP-Array (Photo-activatable-Ribonucleoside-Enhanced Crosslinking-Immunoprecipitation and Microarray Hybridization) for global identification of Ago-associated miRNAs and their mRNA-targets. On average 25% of mRNAs in AML cell lines bearing the AML1/ETO or PML/RARα translocation were identified in Argonaute complexes and carry at least one miRNA binding site and thus are under miRNA control. 60% and 27% of miRNAs and mRNAs, respectively, overlap between the four analyzed Argonaute proteins, while 50% and 52% (46 miRNAs and 241 mRNAs) were associated with one Argonaute protein specifically. However, pathway classification of Ago-associated target-mRNAs indicate more than 90% overlap between the Argonaute proteins and thus are indicative of a concerted action of these four proteins in 150 pathways identified. Moreover, miR-181a/b, up-regulated in t(15;17)-positive AML patients, were detected in association with the four human Argonaute proteins in NB4 cells and show binding sites for the protein kinase PDPK1 potentially leading to inhibition of AKT, whereas eight other Ago-associated miRNA sequence families (seqgrp-miR-98, −130a, −19a, −25, −27a, −301a, −361 and −320) in association with Ago3 are able to repress the upstream tumor suppressor TSC1 leading to activation of the mTOR pathway and increased cell growth. In addition, the repression of the MAP kinase phosphatase DUSP6 by four Ago-associated miRNA sequence families (seqgrp-miR-29a, −17, −125a and −98) leads to activation of proliferative genes in the MAPK pathway of both, t(8;21)- and t(15;17)-positive AML. In summary, miRNAs represent suitable biomarkers for differentiation of AML subtypes of pediatric AML patients. Furthermore, our studies show that the four human Argonaute proteins cooperate in the regulation of AML-relevant signaling pathways providing new insights into AML biology and may present the starting point for novel therapeutic interventions. Disclosures: No relevant conflicts of interest to declare.


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