Integrated Analysis of a Competing Endogenous RNA Network Reveals a Prognostic lncRNA Signature in Bladder Cancer

Long non-coding RNAs (lncRNAs) act as competing endogenous RNAs (ceRNAs) to regulate mRNA expression through sponging microRNA in tumorigenesis and progression. However, following the discovery of new RNA interaction, the differentially expressed RNAs and ceRNA regulatory network are required to update. Our study comprehensively analyzed the differentially expressed RNA and corresponding ceRNA network and thus constructed a potentially predictive tool for prognosis. “DESeq2” was used to perform differential expression analysis. Two hundred and six differentially expressed (DE) lncRNAs, 222 DE miRNAs, and 2,463 DE mRNAs were found in this study. The lncRNA-mRNA interactions in the miRcode database and the miRNA-mRNA interactions in the starBase, miRcode, and mirTarBase databases were searched, and a competing endogenous RNA (ceRNA) network with 186 nodes and 836 interactions was subsequently constructed. Aberrant expression patterns of lncRNA NR2F1-AS1 and lncRNA AC010168.2 were evaluated in two datasets (GSE89006, GSE31684), and real-time polymerase chain reaction was also performed to validate the expression pattern. Furthermore, we found that these two lncRNAs were independent prognostic biomarkers to generate a prognostic lncRNA signature by univariate and multivariate Cox analyses. According to the lncRNA signature, patients in the high-risk group were associated with a poor prognosis and validated by an external dataset. A novel genomic-clinicopathologic nomogram to improve prognosis prediction of bladder cancer was further plotted and calibrated. Our study deepens the understanding of the regulatory ceRNA network and provides an easy-to-do genomic-clinicopathological nomogram to predict the prognosis in patients with bladder cancer.

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An integrated analysis of the competing endogenous RNA network and co-expression network revealed seven hub long non-coding RNAs in osteoarthritis

Bone and Joint Research ◽

10.1302/2046-3758.93.bjr-2019-0140.r2 ◽

2020 ◽

Vol 9 (3) ◽

pp. 90-98 ◽

Cited By ~ 1

Author(s):

Haitao Chen ◽

Liaobin Chen

Keyword(s):

Extracellular Matrix ◽

Expression Profiles ◽

Osteoclast Differentiation ◽

Signalling Pathway ◽

Differentially Expressed ◽

Integrated Analysis ◽

Knee Cartilage ◽

Competing Endogenous Rna ◽

Cerna Network ◽

Non Coding Rnas

Aims This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network. Methods Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs. Results We detected 1,212 DEmRNAs and 49 DElncRNAs in OA and normal knee cartilage. A total of 75 dysregulated lncRNA-miRNA interactions and 711 dysregulated miRNA-mRNA interactions were obtained in the ceRNA network, including ten DElncRNAs, 69 miRNAs, and 72 DEmRNAs. Similarly, 1,330 dysregulated lncRNA-mRNA interactions were used to construct the co-expression network, which included ten lncRNAs and 407 mRNAs. We finally identified seven hub lncRNAs, named MIR210HG, HCP5, LINC00313, LINC00654, LINC00839, TBC1D3P1-DHX40P1, and ISM1-AS1. Subsequent enrichment analysis elucidated that these lncRNAs regulated extracellular matrix organization and enriched in osteoclast differentiation, the FoxO signalling pathway, and the tumour necrosis factor (TNF) signalling pathway in the development of OA. Conclusion The integrated analysis of the ceRNA network and co-expression network identified seven hub lncRNAs associated with OA. These lncRNAs may regulate extracellular matrix changes and chondrocyte homeostasis in OA progress. Cite this article: Bone Joint Res. 2020;9(3):90–98.

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Genome-Wide Analysis of the miRNA–mRNAs Network Involved in Cold Tolerance in Populus simonii × P. nigra

Genes ◽

10.3390/genes10060430 ◽

2019 ◽

Vol 10 (6) ◽

pp. 430 ◽

Cited By ~ 3

Author(s):

Bo Zhou ◽

Yutong Kang ◽

Jingtong Leng ◽

Qijiang Xu

Keyword(s):

Cold Tolerance ◽

High Throughput Sequencing ◽

Expression Patterns ◽

Differential Expression Analysis ◽

Chilling Injury ◽

Cold Treatment ◽

Differentially Expressed ◽

Integrated Analysis ◽

Populus Simonii ◽

Cold Induction

Background: Cold tolerance is important for plants’ geographical distribution and survival in extreme seasonal variations of climate. However, Populus simonii × P. nigra shows wide adaptability and strong cold resistance. Transcriptional and post-transcriptional regulation of cold-responsive genes is crucial for cold tolerance in plants. To understand the roles of regulatory RNAs under cold induction in Populus simonii × P. nigra, we constructed cDNA and small RNA libraries from leaf buds treated or not with −4 °C for 8 h for analysis. Results: Through high-throughput sequencing and differential expression analysis, 61 miRNAs and 1229 DEGs were identified under cold induction condition in Populus simonii × P. nigra. The result showed that miR167a, miR1450, miR319a, miR395b, miR393a-5p, miR408-5p, and miR168a-5p were downregulated, whereas transcription level of miR172a increased under the cold treatment. Thirty-one phased-siRNA were also obtained (reads ≥ 4) and some of them proceeded from TAS3 loci. Analysis of the differentially expressed genes (DEGs) showed that transcription factor genes such as Cluster-15451.2 (putative MYB), Cluster-16493.29872 (putative bZIP), Cluster-16493.29175 (putative SBP), and Cluster-1378.1 (putative ARF) were differentially expressed in cold treated and untreated plantlets of Populus simonii × P. nigra. Integrated analysis of miRNAs and transcriptome showed miR319, miR159, miR167, miR395, miR390, and miR172 and their target genes, including MYB, SBP, bZIP, ARF, LHW, and ATL, were predicted to be involved in ARF pathway, SPL pathway, DnaJ related photosystem II, and LRR receptor kinase, and many of them are known to resist chilling injury. Particularly, a sophisticated regulatory model including miRNAs, phasiRNAs, and targets of them was set up. Conclusions: Integrated analysis of miRNAs and transcriptome uncovered the complicated regulation of the tolerance of cold in Populus simonii × P. nigra. MiRNAs, phasiRNAs, and gene-encoded transcription factors were characterized at a whole genome level and their expression patterns were proved to be complementary. This work lays a foundation for further research of the pathway of sRNAs and regulatory factors involved in cold tolerance.

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Comprehensive Analysis of a ceRNA Network Reveals Potential Prognostic lncRNAs Involved in Progression of Bladder Cancer

10.21203/rs.3.rs-434872/v1 ◽

2021 ◽

Author(s):

Dehua Ou ◽

Zesong Wu ◽

Peilin Shen ◽

Yingkai Hong ◽

Si Chen ◽

...

Keyword(s):

Bladder Cancer ◽

Risk Score ◽

Cox Model ◽

Expression Profiles ◽

Training Group ◽

Survival Prediction ◽

Competing Endogenous Rna ◽

Aberrant Expression ◽

Cerna Network ◽

Risk Patients

Abstract Background: The aberrant expression of long non-coding RNAs (lncRNAs) has attracted more and more attention in the biological field of bladder cancer(BC). We aim to construct a competing endogenous RNA(ceRNA) network reveals potential prognostic lncRNAs involved in progression of BC.Results: Expression profiles of messenger RNA(mRNA), micro RNA(miRNA) and lncRNA of 397 BC samples and 19 non-tumor tissues were downloaded from The Cancer Genome Atlas(TCGA) database. Patients with BC were randomly divided into training group (n=198) and validation group (n=199). Then, 130 lncRNAs, 159 miRNAs and 2,048 mRNAs were identified as differentially expressed genes (DEGs, |logFC|>1, FDR<0.01) related to BC progression. Nextly, we constructed an BC associated deregulated competing endogenous RNA(ceRNA) network with 70 lncRNAs, 30 miRNAs, and 62 mRNAs involved in. Subsequently, a seven-lncRNA signature was constructed by establishing a LASSO Cox model with 13 lncRNAs associated with survival from the ceRNA network. This signature can well distinguish high-risk patients from low-risk patients in training group and verification group. Furthermore, we combined the risk score model with other clinical fictures to estimate the ability of survival prediction. The result suggested that the risk score can be selected as an independent prognostic factor for overall survival(OS) rate. Conclusion: In this study, we construct a ceRNA network related to progression of BC and established an seven-lncRNA signature, which was a candidate prognostic biomarker for prognostic prediction of BC patients .

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Identifying an lncRNA-Related ceRNA Network to Reveal Novel Targets for a Cutaneous Squamous Cell Carcinoma

Biology ◽

10.3390/biology10050432 ◽

2021 ◽

Vol 10 (5) ◽

pp. 432

Author(s):

Yaqin Xu ◽

Yingying Dong ◽

Yunhua Deng ◽

Qianrong Qi ◽

Mi Wu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Biological Process ◽

Normal Skin ◽

Expression Patterns ◽

Therapeutic Targets ◽

Cutaneous Squamous Cell Carcinoma ◽

Differentially Expressed ◽

Cerna Network

A cutaneous squamous cell carcinoma (cSCC) derived from keratinocytes is the second most common cause of non-melanoma skin cancer. The accumulation of the mutational burden of genes and cellular DNA damage caused by the risk factors (e.g., exposure to ultraviolet radiation) contribute to the aberrant proliferation of keratinocytes and the formation of a cSCC. A cSCC encompasses a spectrum of diseases that range from recursor actinic keratosis (AK) and squamous cell carcinoma (SCC) in situ (SCCIS) to invasive cSCCs and further metastatic SCCs. Emerging evidence has revealed that lncRNAs are involved in the biological process of a cSCC. According to the ceRNA regulatory theory, lncRNAs act as natural miRNA sponges and interact with miRNA response elements, thereby regulating the mRNA expression of their down-stream targets. This study was designed to search for the potential lncRNAs that may become potential therapeutic targets or biomarkers of a cSCC. Considering the spirit of the study to be adequately justified, we collected microarray-based datasets of 19 cSCC tissues and 12 normal skin samples from the GEO database (GSE42677 and GSE45164). After screening the differentially expressed genes via a limma package, we identified 24 differentially expressed lncRNAs (DElncRNAs) and 3221 differentially expressed mRNAs (DEmRNAs). The miRcode, miRTarBase, miRDB and TargetScan databases were used to predict miRNAs that could interact with DElncRNAs and DEmRNAs. A total of 137 miRNA-lncRNA and 221 miRNA-mRNA pairs were retained in the ceRNA network, consisting of 31 miRNAs, 11 DElncRNAs and 155 DEmRNAs. For the functional analysis, the top enriched biological process was enhancer sequence-specific DNA binding in Gene Ontology (GO) terms. The FoxO signaling pathway, autophagy and cellular senescence were the top enrichment terms based on a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The combination of a STRING tool and Cytoscape software (plug-in MCODE) identified five core mRNAs and built a core mRNA-associated ceRNA network. The expression for five identified core mRNAs and their related nine lncRNAs was validated using the external dataset GSE7553. Finally, one lncRNA HLA-F-AS1 and three mRNAs named AGO4, E2F1 and CCND1 were validated with the same expression patterns. We speculate that lncRNA HLA-F-AS1 may sponge miR-17-5p or miR-20b-5p to regulate the expression of CCND1 and E2F1 in the cSCC. The present study may provide potential diagnostic and therapeutic targets for cSCC patients.

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Integrated Analysis of Liver Transcriptome, miRNA, and Proteome of Chinese Indigenous Breed Ningxiang Pig in Three Developmental Stages Uncovers Significant miRNA–mRNA–Protein Networks in Lipid Metabolism

Frontiers in Genetics ◽

10.3389/fgene.2021.709521 ◽

2021 ◽

Vol 12 ◽

Author(s):

Biao Li ◽

Jinzeng Yang ◽

Yan Gong ◽

Yu Xiao ◽

Qinghua Zeng ◽

...

Keyword(s):

Lipid Metabolism ◽

Expression Patterns ◽

Immune Defense ◽

Differentially Expressed ◽

Integrated Analysis ◽

Liver Development ◽

Liver Growth ◽

Functional Transformation ◽

Functional Changes ◽

Glycolipid Metabolism

Liver is an important metabolic organ of mammals. During each transitional period of life, liver metabolism is programmed by a complex molecular regulatory system for multiple physiological functions, many pathways of which are regulated by hormones and cytokines, nuclear receptors, and transcription factors. To gain a comprehensive and unbiased molecular understanding of liver growth and development in Ningxiang pigs, we analyzed the mRNA, microRNA (miRNA), and proteomes of the livers of Ningxiang pigs during lactation, nursery, and fattening periods. A total of 22,411 genes (19,653 known mRNAs and 2758 novel mRNAs), 1122 miRNAs (384 known miRNAs and 738 novel miRNAs), and 1123 unique proteins with medium and high abundance were identified by high-throughput sequencing and mass spectrometry. We show that the differences in transcriptional, post-transcriptional, or protein levels were readily identified by comparing different time periods, providing evidence that functional changes that may occur during liver development are widespread. In addition, we found many overlapping differentially expressed genes (DEGs)/differentially expressed miRNAs (DEMs)/differentially expressed proteins (DEPs) related to glycolipid metabolism in any group comparison. These overlapping DEGs/DEMs/DGPs may play an important role in functional transformation during liver development. Short Time-series Expression Miner (STEM) analysis revealed multiple expression patterns of mRNA, miRNA, and protein in the liver. Furthermore, several diverse key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including immune defense, glycolipid metabolism, protein transport and uptake, and cell proliferation and development, were identified by combined analysis of DEGs and DGPs. A number of predicted miRNA–mRNA–protein pairs were found and validated by qRT-PCR and parallel reaction monitoring (PRM) assays. The results provide new and important information about the genetic breeding of Ningxiang pigs, which represents a foundation for further understanding the molecular regulatory mechanisms of dynamic development of liver tissue, functional transformation, and lipid metabolism.

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Integrated analysis of coexpression and competitive endogenous RNA networks identified survival-related genes in gastrointestinal tumors

10.21203/rs.3.rs-331336/v1 ◽

2021 ◽

Author(s):

Dan Bai ◽

Huhu Feng ◽

Jiajun Yang ◽

Haitao Shi ◽

Fanpu Ji ◽

...

Keyword(s):

Cox Regression ◽

Expression Patterns ◽

Curve Analysis ◽

Guanosine Monophosphate ◽

Gastrointestinal Tumors ◽

Integrated Analysis ◽

Cox Regression Analysis ◽

Cerna Network ◽

Diagnosis And Prognosis ◽

Competitive Endogenous Rna

Abstract Early diagnosis and prognosis rely on the successful identification of biomarkers and understanding the mechanisms. Through pan-cancer analysis amongst three types of gastrointestinal tumors, we constructed competitive endogenous RNA (ceRNA) networks, differentially expressed set of genes were distinguished, validated, and analyzed, their relevance to survival elucidated with immune infiltration profiles. Shared genes in esophageal, gastric and colon cancers were found significantly enriched in the processes of cell cycle, cell differentiation, DNA replication, synaptic transmission, the cyclic guanosine monophosphate protein-dependent protein kinase (cGMP-PKG) signaling pathway, and the glutamate receptor and other functions. Principal component analysis of the ceRNA network suggested the expression patterns of identified genes. Using Cox regression analysis of mRNAs, miRNAs and lncRNAs in the ceRNA network, genes including hsa-mir-196b, hsa-mir-584, PPP1R12B, SYNM, PDE2A, ALDH6A1 and MIR22HG were found significantly survival-related. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) showed that the identified genes were not related to the survival in thyroid nor breast cancers, but effective for the prognosis of gastrointestinal tumors. These results could provide new theoretical and experimental clues, unravel the mechanisms, assisting molecular diagnosis and prognosis of gastrointestinal tumors.

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Construction and Comprehensive Analysis of Dysregulated Long Noncoding RNA-Associated Competing Endogenous RNA Network in Moyamoya Disease

Computational and Mathematical Methods in Medicine ◽

10.1155/2020/2018214 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Xuefeng Gu ◽

Dongyang Jiang ◽

Yue Yang ◽

Peng Zhang ◽

Guoqing Wan ◽

...

Keyword(s):

Moyamoya Disease ◽

Cerebral Artery ◽

Regulatory Network ◽

Noncoding Rna ◽

Expression Profiles ◽

Differentially Expressed ◽

Competing Endogenous Rna ◽

Cerna Network ◽

And Control ◽

Control Samples

Background. Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by chronic progressive stenosis or occlusion of the bilateral internal carotid artery (ICA), the anterior cerebral artery (ACA), and the middle cerebral artery (MCA). MMD is secondary to the formation of an abnormal vascular network at the base of the skull. However, the etiology and pathogenesis of MMD remain poorly understood. Methods. A competing endogenous RNA (ceRNA) network was constructed by analyzing sample-matched messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA) expression profiles from MMD patients and control samples. Then, a protein-protein interaction (PPI) network was constructed to identify crucial genes associated with MMD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were employed with the DAVID database to investigate the underlying functions of differentially expressed mRNAs (DEmRNAs) involved in the ceRNA network. CMap was used to identify potential small drug molecules. Results. A total of 94 miRNAs, 3649 lncRNAs, and 2294 mRNAs were differentially expressed between MMD patients and control samples. A synergistic ceRNA lncRNA-miRNA-mRNA regulatory network was constructed. Core regulatory miRNAs (miR-107 and miR-423-5p) and key mRNAs (STAT5B, FOSL2, CEBPB, and CXCL16) involved in the ceRNA network were identified. GO and KEGG analyses indicated that the DEmRNAs were involved in the regulation of the immune system and inflammation in MMD. Finally, two potential small molecule drugs, CAY-10415 and indirubin, were identified by CMap as candidate drugs for treating MMD. Conclusions. The present study used bioinformatics analysis of candidate RNAs to identify a series of clearly altered miRNAs, lncRNAs, and mRNAs involved in MMD. Furthermore, a ceRNA lncRNA-miRNA-mRNA regulatory network was constructed, which provides insights into the novel molecular pathogenesis of MMD, thus giving promising clues for clinical therapy.

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Integrated analysis identifies a pathway-related competing endogenous RNA network in the progression of pancreatic cancer

BMC Cancer ◽

10.1186/s12885-020-07470-4 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Fuqiang Zu ◽

Peng Liu ◽

Huaitao Wang ◽

Ting Zhu ◽

Jian Sun ◽

...

Keyword(s):

Pancreatic Cancer ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Tumor Formation ◽

Functional Enrichment ◽

Integrated Analysis ◽

Competing Endogenous Rna ◽

Hub Genes ◽

Cerna Network ◽

Competing Endogenous Rna Network

Abstract Background It is well acknowledged that cancer-related pathways play pivotal roles in the progression of pancreatic cancer (PC). Employing Integrated analysis, we aim to identify the pathway-related ceRNA network associated with PC progression. Methods We divided eight GEO datasets into three groups according to their platform, and combined TCGA and GTEx databases as a group. Additionally, we screened out the differentially expressed genes (DEGs) and performed functional enrichment analysis in each group, and recognized the top hub genes in the most enriched pathway. Furthermore, the upstream of miRNAs and lncRNAs were predicted and validated according to their expression and prognostic roles. Finally, the co-expression analysis was applied to identify a pathway-related ceRNA network in the progression of PC. Results A total of 51 significant pathways that common enriched in all groups were spotted. Enrichment analysis indicated that pathway in cancer was greatly linked with tumor formation and progression. Next, the top 20 hug genes in this pathway were recognized, and stepwise prediction and validation from mRNA to lncRNA, including 11 hub genes, 4 key miRNAs, and 2 key lncRNAs, were applied to identify a meaningful ceRNA network according to ceRNA rules. Ultimately, we identified the PVT1/miR-20b/CCND1 axis as a promising pathway-related ceRNA axis in the progression of PC. Conclusion Overall, we elucidate the pathway-related ceRNA regulatory network of PVT1/miR-20b/CCND1 in the progression of PC, which can be considered as therapeutic targets and encouraging prognostic biomarkers for PC.

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Integrated Analysis of Long Noncoding RNA and Coding RNA Expression in Esophageal Squamous Cell Carcinoma

International Journal of Genomics ◽

10.1155/2013/480534 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 22

Author(s):

Wei Cao ◽

Wei Wu ◽

Fachun Shi ◽

Xiaobing Chen ◽

Lihua Wu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Noncoding Rna ◽

Cell Cancer ◽

Differentially Expressed ◽

Integrated Analysis ◽

Aberrant Expression ◽

A Genome

Tumorigenesis is a complex dynamic biological process that includes multiple steps of genetic and epigenetic alterations, aberrant expression of noncoding RNA, and changes in the expression profiles of coding genes. We call the collection of those perturbations in genome space the “cancer initiatome.” Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome and they have key regulatory functions in chromatin remodeling and gene expression. Spatiotemporal variation in the expression of lncRNAs has been observed in development and disease states, including cancer. A few dysregulated lncRNAs have been studied in cancers, but the role of lncRNAs in the cancer initiatome remains largely unknown, especially in esophageal squamous cell carcinoma (ESCC). We conducted a genome-wide screen of the expression of lncRNAs and coding RNAs from ESCC and matched adjacent nonneoplastic normal tissues. We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis. Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC. These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer.

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Immune-related miRNA-mRNA regulation network in the livers of DHAV-3-infected ducklings

10.21203/rs.2.13422/v3 ◽

2019 ◽

Author(s):

Fengyao Wu ◽

Fengying Lu ◽

Xin Fan ◽

Jin Chao ◽

Chuanmin Liu ◽

...

Keyword(s):

Signaling Pathways ◽

High Throughput Sequencing ◽

Expression Patterns ◽

Differentially Expressed ◽

Receptor Interaction ◽

Integrated Analysis ◽

Mrna Regulation ◽

Duck Hepatitis ◽

Differentially Expressed Mirnas ◽

Regulation Network

Abstract Background: Duck hepatitis A virus type 3 (DHAV-3) is one of the most harmful pathogens in the duck industry. However, the molecular mechanism underlying DHAV-3 infection in ducklings is remain poorly understood. To elucidate the genetic regulatory network for miRNA-mRNA and the signaling pathways involved in DHAV-3 infection in ducklings, we conducted global miRNA and mRNA expression profiling of duckling liver tissues infected with lethal DHAV-3 using high-throughput sequencing. Results: We found 156 differentially expressed miRNAs (DEMs) and 7717 differentially expressed miRNAs (DEGs) between mock-infected and DHAV-3-infected duckling livers. A total of 19,606 miRNA-mRNA pairs with negatively correlated expression patterns were identified in miRNA-mRNA networks constructed on the basis of these DEMs and DEGs. Moreover, immune-related pathways including the cytokine-cytokine receptor interaction, apoptosis, Toll-like receptor, Jak-STAT, and RIG-I-like receptor signaling pathway were significantly enriched through analyzing functions of mRNAs in the network in response to DHAV-3 infection. Besides, apl-miR-32-5p, apl-miR-125-5p, apl-miR-128-3p, apl-miR-460-5p, and novel-m0012-3p were identified as potential regulators in the immune-related signaling pathways during the DHAV-3 infection. Conclusions: To our knowledge, this is the first report on integrated analysis of miRNA-seq and mRNA-seq in DHAV-3-infected ducklings. The results indicated the important roles of miRNAs in regulating immune response genes and revealed the immune related miRNA-mRNA regulation network in the DHAV-3-infected duckling liver. Our findings may provide valuable information to further investigate the roles of miRNAs and their target genes in DHAV-3 replication and pathogenesis; additionally, they may offer clues for further understanding host-virus interactions.

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