Identifying Differentially Expressed MicroRNAs, Target Genes, and Key Pathways Deregulated in Patients with Liver Diseases

Liver diseases are important causes of morbidity and mortality worldwide. The aim of this study was to identify differentially expressed microRNAs (miRNAs), target genes, and key pathways as innovative diagnostic biomarkers in liver patients with different pathology and functional state. We determined, using RT-qPCR, the expression of 472 miRNAs in 125 explanted livers from subjects with six different liver pathologies and from control livers. ANOVA was employed to obtain differentially expressed miRNAs (DEMs), and miRDB (MicroRNA target prediction database) was used to predict target genes. A miRNA–gene differential regulatory (MGDR) network was constructed for each condition. Key miRNAs were detected using topological analysis. Enrichment analysis for DEMs was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We identified important DEMs common and specific to the different patient groups and disease progression stages. hsa-miR-1275 was universally downregulated regardless the disease etiology and stage, while hsa-let-7a*, hsa-miR-195, hsa-miR-374, and hsa-miR-378 were deregulated. The most significantly enriched pathways of target genes controlled by these miRNAs comprise p53 tumor suppressor protein (TP53)-regulated metabolic genes, and those involved in regulation of methyl-CpG-binding protein 2 (MECP2) expression, phosphatase and tensin homolog (PTEN) messenger RNA (mRNA) translation and copper homeostasis. Our findings show a novel panel of deregulated miRNAs in the liver tissue from patients with different liver pathologies. These miRNAs hold potential as biomarkers for diagnosis and staging of liver diseases.

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Identification of Potential Biomarkers and Biological Pathways in Juvenile Dermatomyositis Based on miRNA-mRNA Network

BioMed Research International ◽

10.1155/2019/7814287 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Cheng-Cheng Qiu ◽

Qi-Sheng Su ◽

Shang-Yong Zhu ◽

Ruo-Chuan Liu

Keyword(s):

Regulatory Network ◽

Messenger Rna ◽

Target Genes ◽

Juvenile Dermatomyositis ◽

Type I Diabetes ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Type I ◽

Ppi Network ◽

Potential Biomarkers

Objective. The aim of this study is to explore the potential pathogenesis of juvenile dermatomyositis by bioinformatics analysis of gene chips, which would screen the hub genes, identify potential biomarkers, and reveal the development mechanism of juvenile dermatomyositis. Material and Methods. We retrieved juvenile dermatomyositis’s original expression microarray data of message RNAs (mRNAs) and microRNAs (miRNAs) from NCBI’s Gene Expression Omnibus database (GEO, http://www.ncbi.nlm.nih.gov/geo/); through the R package of limma in Bioconductor, we can screen the differentially expressed miRNAs and mRNAs, and then we further analyzed the predicted target genes by the methods such as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and miRNA-mRNA regulatory network construction and protein-protein interaction (PPI) network using Cytoscape 3.6.1. Results. Compared with normal juvenile skin tissues, 6 upregulated microRNAs and 5 downregulated microRNAs were identified from 166 downregulated microRNAs and 58 upregulated microRNAs in juvenile dermatomyositis tissues. The enrichment pathways of differentially expressed microRNAs include cell adhesion molecules (CAMs), autoimmune thyroid disease, Type I diabetes mellitus, antigen and presentation, viral myocardium, graft-versus-host disease, and Kaposi sarcoma-associated herpes virus infection. By screening of microRNA-messenger RNA regulatory network and construction of PPI network map, three target miRNAs were identified, namely, miR-193b, miR-199b-5p, and miR-665. Conclusion. We identified mir-193b, mir-199b-5p, and mir-6653 target miRNAs by exploring the miRNA-mRNA regulation network mechanism related to the pathogenesis of juvenile dermatomyositis, which will be of great significance for further study on the pathogenesis and targeted therapy of juvenile dermatomyositis.

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Construction of a Potential Breast Cancer-Related miRNA-mRNA Regulatory Network

BioMed Research International ◽

10.1155/2020/6149174 ◽

2020 ◽

Vol 2020 ◽

pp. 1-18

Author(s):

Xinhong Liu ◽

Feng Chen ◽

Fang Tan ◽

Fang Li ◽

Ruokun Yi ◽

...

Keyword(s):

Breast Cancer ◽

Transcription Factors ◽

Target Genes ◽

Differential Expression Analysis ◽

Mirna Gene ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Epithelial Tissue ◽

Hub Genes ◽

Geo Database

Background. Breast cancer is a malignant tumor that occurs in the epithelial tissue of the breast gland and has become the most common malignancy in women. The regulation of the expression of related genes by microRNA (miRNA) plays an important role in breast cancer. We constructed a comprehensive breast cancer-miRNA-gene interaction map. Methods. Three miRNA microarray datasets (GSE26659, GSE45666, and GSE58210) were obtained from the GEO database. Then, the R software “LIMMA” package was used to identify differential expression analysis. Potential transcription factors and target genes of screened differentially expressed miRNAs (DE-miRNAs) were predicted. The BRCA GE-mRNA datasets (GSE109169 and GSE139038) were downloaded from the GEO database for identifying differentially expressed genes (DE-genes). Next, GO annotation and KEGG pathway enrichment analysis were conducted. A PPI network was then established, and hub genes were identified via Cytoscape software. The expression and prognostic roles of hub genes were further evaluated. Results. We found 6 upregulated differentially expressed- (DE-) miRNAs and 18 downregulated DE-miRNAs by analyzing 3 Gene Expression Omnibus databases, and we predicted the upstream transcription factors and downstream target genes for these DE-miRNAs. Then, we used the GEO database to perform differential analysis on breast cancer mRNA and obtained differentially expressed mRNA. We found 10 hub genes of upregulated DE-miRNAs and 10 hub genes of downregulated DE-miRNAs through interaction analysis. Conclusions. In this study, we have performed an integrated bioinformatics analysis to construct a more comprehensive BRCA-miRNA-gene network and provide new targets and research directions for the treatment and prognosis of BRCA.

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Role of miRNAs in Sigmoid Colon Cancer: A Search for Potential Biomarkers

Cancers ◽

10.3390/cancers12113311 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3311

Author(s):

Diego Marques ◽

Layse Raynara Ferreira-Costa ◽

Lorenna Larissa Ferreira-Costa ◽

Ana Beatriz Bezerra-Oliveira ◽

Romualdo da Silva Correa ◽

...

Keyword(s):

Colon Cancer ◽

Sigmoid Colon ◽

Cancer Progression ◽

Target Genes ◽

Mirna Gene ◽

Differentially Expressed ◽

Sigmoid Colon Cancer ◽

Colon Tissue ◽

Aberrant Expression ◽

Differentially Expressed Mirnas

The aberrant expression of microRNAs in known to play a crucial role in carcinogenesis. Here, we evaluated the miRNA expression profile of sigmoid colon cancer (SCC) compared to adjacent-to-tumor (ADJ) and sigmoid colon healthy (SCH) tissues obtained from colon biopsy extracted from Brazilian patients. Comparisons were performed between each group separately, considering as significant p-values < 0.05 and |Log2(Fold-Change)| > 2. We found 20 differentially expressed miRNAs (DEmiRNAs) in all comparisons, two of which were shared between SCC vs. ADJ and SCC vs. SCH. We used miRTarBase, and miRTargetLink to identify target-genes of the differentially expressed miRNAs, and DAVID and REACTOME databases for gene enrichment analysis. We also used TCGA and GTEx databases to build miRNA-gene regulatory networks and check for the reproducibility in our results. As findings, in addition to previously known miRNAs associated with colorectal cancer, we identified three potential novel biomarkers. We showed that the three types of colon tissue could be clearly distinguished using a panel composed by the 20 DEmiRNAs. Additionally, we found enriched pathways related to the carcinogenic process in which miRNA could be involved, indicating that adjacent-to-tumor tissues may be already altered and cannot be considered as healthy tissues. Overall, we expect that these findings may help in the search for biomarkers to prevent cancer progression or, at least, allow its early detection, however, more studies are needed to confirm our results.

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Transcriptome analysis of messenger RNA and long noncoding RNA related to different developmental stages of tail adipose tissues of sunite sheep

10.21203/rs.3.rs-131480/v1 ◽

2020 ◽

Author(s):

Xige He ◽

Rihan Wu ◽

Yueying Yun ◽

Xia Qin ◽

Lu Chen ◽

...

Keyword(s):

Long Noncoding Rna ◽

Messenger Rna ◽

Noncoding Rna ◽

Target Genes ◽

Early Stage ◽

Expression Profiles ◽

Theoretical Data ◽

Differentially Expressed ◽

Growth Stages ◽

Complex Biological Process

Abstract Background: Sunite sheep are a fat-tailed sheep species with a low percentage of intramuscular fat and good quality lean meat, and their tail fat can be used as a source of dietary fat by humans. To understand the potential regulatory mechanism of different growth stages of tail fat in Sunite sheep, we performed high-throughput RNA sequencing to characterize the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles of the sheep tail fat at the age of 6 months, 18 months, and 30 months.Results: A total of 223 differentially expressed genes (DEGs) and 148 differentially expressed lncRNAs were found in the tail fat of 6-, 18-, and 30-month-old sheep (false discovery rate < 0.05, |Fold Change| ≥ 2). Based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, we found that fat-related DEGs were mainly expressed at 6 months of age, and gradually decreased at 18 and 30 months of age. The target gene prediction analysis shows that most of the lncRNAs target more than 20 mRNAs as their trans-regulators (53 mRNAs at most). Further, we obtained several fat-related differentially-expressed target genes; these target genes interact with different differentially expressed lncRNAs at various ages and play an important role in the development of tail fat. Based on the DEGs and differentially expressed lncRNAs, we established three co-expression networks for each comparison group. Conclusions: Finally, we conclude that the development of the sheep tail fat is more active during the early stage of growth and gradually decreases with the increase in age. The mutual regulation of lncRNAs and mRNAs may play a key role in this complex biological process, and our findings will provide some basic theoretical data for future studies on tail fat development of fat-tailed sheep.

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Identification and characterization of heat-responsive microRNAs at the booting stage in two rice varieties 9311 and Nagina 22

Genome ◽

10.1139/gen-2020-0175 ◽

2021 ◽

Author(s):

Ying Luo ◽

Tao Wang ◽

Dan Yang ◽

Biao Luo ◽

Weiping Wang ◽

...

Keyword(s):

Stress Responses ◽

High Throughput Sequencing ◽

Target Genes ◽

Elevated Temperatures ◽

Differentially Expressed ◽

Control Group ◽

Microrna Target ◽

Rice Varieties ◽

Booting Stage ◽

Differentially Expressed Mirnas

Abstract: MicroRNAs (miRNAs) are small, non-coding, regulatory RNAs that play important roles in abiotic stress responses in plants. but their regulatory roles in the adaptive response to heat stress at the booting stage in two rice varieties 9311 and Nagina 22, remain largely unknown. In this study, 464 known miRNAs and 123 potential novel miRNAs were identified. Of these miRNAs, a total of 90 differential expressed miRNAs were obtained with 9311 libraries as control group, of which 54 upregulated and 36 downregulated miRNAs. To gain insight into functional significance, 2773 potential target genes of these 90 differentially expressed miRNAs were predicted. GO enrichment showed that the predicted target genes of differentially expressed miRNAs including NACs, LACs, CSD, and Hsp40. KEGG pathway analysis showed that target genes of these differentially expressed miRNAs were significantly enriched in plant hormone signal transduction pathway. The expression levels of ten differentially expressed miRNAs and their target genes obtained by qRT-PCR were largely consistent with the sequencing results. This study lays a foundation for the elucidation of the miRNA-mediated regulatory mechanism in rice at elevated temperatures. Key words: rice, heat-responsive, microRNA, target gene, booting stage, high-throughput sequencing

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Genome-wide identification and comparison of differentially expressed profiles of miRNAs and lncRNAs with associated ceRNA networks in the gonads of Chinese soft-shelled turtle, Pelodiscus sinensis

10.21203/rs.2.10525/v4 ◽

2020 ◽

Author(s):

Xiao Ma ◽

Shuangshuang Cen ◽

Luming Wang ◽

Chao Zhang ◽

Limin Wu ◽

...

Keyword(s):

Messenger Rna ◽

Target Genes ◽

Expression Profiles ◽

Differentially Expressed ◽

Integrated Analysis ◽

Pelodiscus Sinensis ◽

Specific Expression ◽

Protein Coding ◽

Reproductive Regulation ◽

Protein Coding Genes

Abstract Background: The gonad is the major factor affecting animal reproduction. The regulatory mechanism of the expression of protein-coding genes involved in reproduction still remains to be elucidated. Increasing evidence has shown that ncRNAs play key regulatory roles in gene expression in many life processes. The roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in reproduction have been investigated in some species. However, the regulatory patterns of miRNA and lncRNA in the sex biased expression of protein coding genes remains to be elucidated. In this study, we performed an integrated analysis of miRNA, messenger RNA (mRNA), and lncRNA expression profiles to explore their regulatory patterns in the female ovary and male testis of Chinese soft-shelled turtle, Pelodiscus sinensis.Results: We identified 10 446 mature miRNAs, 20 414 mRNAs and 28 500 lncRNAs in the ovaries and testes, and 633 miRNAs, 11 319 mRNAs, and 10 495 lncRNAs showed differential expression. A total of 2 814 target genes were identified for miRNAs. The predicted target genes of these differentially expressed (DE) miRNAs and lncRNAs included abundant genes related to reproductive regulation. Furthermore, we found that 189 DEmiRNAs and 5 408 DElncRNAs showed sex-specific expression. Of these, 3 DEmiRNAs and 917 DElncRNAs were testis-specific, and 186 DEmiRNAs and 4 491 DElncRNAs were ovary-specific. We further constructed complete endogenous lncRNA-miRNA-mRNA networks using bioinformatics, including 103 DEmiRNAs, 636 DEmRNAs, and 1 622 DElncRNAs. The target genes for the differentially expressed miRNAs and lncRNAs included abundant genes involved in gonadal development, including Wt1, Creb3l2, Gata4, Wnt2, Nr5a1, Hsd17, Igf2r, H2afz, Lin52, Trim71, Zar1, and Jazf1.Conclusions: In animals, miRNA and lncRNA as master regulators regulate reproductive processes by controlling the expression of mRNAs. Considering their importance, the identified miRNAs, lncRNAs, and their targets in P. sinensis might be useful for studying the molecular processes involved in sexual reproduction and genome editing to produce higher quality aquaculture animals. A thorough understanding of ncRNA-based cellular regulatory networks will aid in the improvement of P. sinensis reproductive traits for aquaculture.

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Differentially Expressed miRNA-Gene Targets Related to Intramuscular Fat in Musculus Longissimus Dorsi of Charolais × Holstein F2-Crossbred Bulls

Genes ◽

10.3390/genes11060700 ◽

2020 ◽

Vol 11 (6) ◽

pp. 700

Author(s):

Bilal Ahmad Mir ◽

Henry Reyer ◽

Katrin Komolka ◽

Siriluck Ponsuksili ◽

Christa Kühn ◽

...

Keyword(s):

Target Genes ◽

Mirna Gene ◽

Target Prediction ◽

Microarray Experiment ◽

Intramuscular Fat ◽

Differentially Expressed ◽

Longissimus Dorsi ◽

P Value ◽

Mirna Expression Pattern ◽

Differentially Expressed Mirnas

Intramuscular fat (IMF) is a meat quality indicator associated with taste and juiciness. IMF deposition, influenced by genetic and non-genetic factors, occurs through a transcriptionally coordinated process of adipogenesis. MicroRNAs (miRNAs) are transcriptional regulators of vital biological processes, including lipid metabolism and adipogenesis. However, in bovines, limited data on miRNA profiling and association with divergent intramuscular fat content, regulated exclusively by genetic parameters, have been reported. Here, a microarray experiment was performed to identify and characterize the miRNA expression pattern in the Musculus longissimus dorsi of F2-cross (Charolais × German Holstein) bulls with high and low IMF. A total of 38 differentially expressed miRNAs (DE miRNAs), including 33 upregulated and 5 downregulated (corrected p-value ≤ 0.05, FC ≥ ±1.2), were reported. Among DE miRNAs, the upregulated miRNAs miR-105a/b, miR-695, miR-1193, miR-1284, miR-1287-5p, miR-3128, miR-3178, miR-3910, miR-4443, miR-4445 and miR-4745, and the downregulated miRNAs miR-877-5p, miR-4487 and miR-4706 were identified as novel fat deposition regulators. DE miRNAs were further analyzed, along with previously identified differentially expressed genes (DEGs) from the same samples and predicted target genes, using multiple bioinformatic approaches, including target prediction tools and co-expression networks, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. We identified DE miRNAs and their gene targets associated with bovine intramuscular adipogenesis, and we provide a basis for further functional investigations.

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microRNA and the pathogenesis of ovarian cancer – a new horizon for molecular diagnostics and treatment?

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2011-0847 ◽

2012 ◽

Vol 50 (4) ◽

Cited By ~ 19

Author(s):

Jan Dominik Kuhlmann ◽

Jens Rasch ◽

Pauline Wimberger ◽

Sabine Kasimir-Bauer

Keyword(s):

Ovarian Cancer ◽

Messenger Rna ◽

Target Genes ◽

Mrna Translation ◽

Ovarian Carcinomas ◽

Rna Molecules ◽

Sequence Complementarity ◽

Functional Understanding ◽

Novel Biomarkers ◽

Gene Regulatory

AbstractOvarian cancer is the leading cause of death among gynecologic malignancies and despite advances in treatment, more than 50% of all patients will experience recurrence, resulting in worse overall prognosis. Therefore, identification of novel biomarkers for ovarian cancer is of significant interest. microRNA (miRNA) constitute a class of small gene regulatory RNA molecules (18–24 nt) and by sequence complementarity, they negatively regulate messenger RNA (mRNA) translation of target genes. Rising data are available that miRNA are functionally involved in the pathogenesis of ovarian cancer. In this regard, recent advances in profiling studies revealed a variety of miRNA candidates, differently expressed in ovarian carcinomas and in disease-specific conditions like hypoxia or chemo-resistance. This review abstracts recent efforts on establishing miRNA as novel molecular biomarkers for ovarian cancer and depicts the existing preliminary framework for defining peripheral-blood derived miRNA as novel circulating biomarkers. Beside these clinical implications, we highlight the current functional understanding of miRNA alteration and discuss major challenges in miRNA profiling approaches. Finally, we briefly outline methodologies to therapeutically modulate miRNA expression in cancer and try to assess how miRNA can improve our conceptual understanding and the clinical management of ovarian cancer.

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Genome-wide profiling of miRNA expression patterns in tubal endometriosis

Reproduction ◽

10.1530/rep-18-0631 ◽

2019 ◽

Vol 157 (6) ◽

pp. 525-534 ◽

Cited By ~ 4

Author(s):

Hang Qi ◽

Guiling Liang ◽

Jin Yu ◽

Xiaofeng Wang ◽

Yan Liang ◽

...

Keyword(s):

Pathway Analysis ◽

Mirna Expression ◽

Gene Networks ◽

Target Genes ◽

Expression Profiles ◽

Expression Patterns ◽

Mirna Gene ◽

Differentially Expressed ◽

Signal Pathways ◽

Differentially Expressed Mirnas

MicroRNA (miRNA) expression proﬁles in tubal endometriosis (EM) are still poorly understood. In this study, we analyzed the differential expression of miRNAs and the related gene networks and signaling pathways in tubal EM. Four tubal epithelium samples from tubal EM patients and five normal tubal epithelium samples from uterine leiomyoma patients were collected for miRNA microarray. Bioinformatics analyses, including Ingenuity Pathway Analysis (IPA), Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) validation of five miRNAs was performed in six tubal epithelium samples from tubal EM and six from control. A total of 17 significantly differentially expressed miRNAs and 4343 potential miRNA-target genes involved in tubal EM were identified (fold change >1.5 and FDR-adjustedPvalue <0.05). IPA indicated connections between miRNAs, target genes and other gynecological diseases like endometrial carcinoma. GO and KEGG analysis revealed that most of the identified genes were involved in the mTOR signaling pathway, SNARE interactions in vesicular transport and endocytosis. We constructed an miRNA-gene-disease network using target gene prediction. Functional analysis showed that the mTOR pathway was connected closely to tubal EM. Our results demonstrate for the first time the differentially expressed miRNAs and the related signal pathways involved in the pathogenesis of tubal EM which contribute to elucidating the pathogenic mechanism of tubal EM-related infertility.

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High-throughput small RNA and transcriptome sequencing reveal reproduction-related microRNAs and mRNA in ovary of Geese in Counter-Season Production

10.21203/rs.2.11246/v1 ◽

2019 ◽

Author(s):

Jin-Shan Ran ◽

Ling-Qian Yin ◽

Jing-Jing Li ◽

Yan-Qiang Tang ◽

Jian Huang ◽

...

Keyword(s):

High Throughput ◽

High Throughput Sequencing ◽

Target Genes ◽

Mirna Gene ◽

Egg Laying ◽

Differentially Expressed ◽

Ovary Development ◽

Regulation Mechanism ◽

Pathway Network ◽

Apoptosis Pathways

Abstract Background Broodiness is a phenomenon that occurs in most avian species and significantly reduces productivity. Several genes are known to play an important role in regulating the progress of reproduction, but the molecular regulation mechanism of broodiness remains unclear. In the current study, via high throughput sequencing, we identified and explored the differentially expressed miRNAs and mRNAs involved in ovarian atrophy. Results We identified a total of 901 mRNAs and 50 miRNAs that were differentially expressed in egg-laying and atrophic ovaries. Among them, numerous DEGs transcripts and target genes for miRNAs were significantly enriched in reproductive processes, cell proliferation, and apoptosis pathways. In addition, a miRNA- gene-pathway network was constructed by considering target relationships and correlation of the expression levels between ovary development-related genes and miRNAs. Conclusions We discovered mRNA and miRNAs transcripts that are candidate regulators of ovary development in broody geese. Our findings expanded our understanding of the functional of miRNAs in ovarian atrophy and demonstrated that RNA-Seq is a powerful tool for examining the molecular mechanism in regulating broodiness.

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