Identification of Novel LncRNA Biomarkers and Construction of LncRNA-Related Networks in Han Chinese Patients with Ischemic Stroke

Background/Aims: Long non-coding RNAs (lncRNAs) are potential biomarkers of tumors, cardiac disease, and cerebral disease because of their interaction with coding RNAs. This work focused on ischemic stroke (IS) and aimed to identify novel lncRNA biomarkers and construct lncRNA-related networks in IS. Methods: Differentially expressed lncRNAs were identified using Arraystar Human LncRNA Microarray v4.0, and validated with qRT-PCR. A lncRNA–mRNA co-expression network and a lncRNA–miRNA–mRNA regulatory network were constructed. Functional and pathway analyses were then performed. Results: In total, 560 up-regulated and 690 down-regulated differentially expressed lncRNAs were found (P < 0.05, false discovery rate < 0.05, absolute fold change ≥ 2). qRT-PCR results confirmed that lncRNA-ENST00000568297, lncRNA-ENST00000568243, and lncRNA-NR_046084 exhibited significant differential expression between IS and controls (all P < 0.05). Areas under the curves (AUCs) for these lncRNAs were 0.733, 0.743, and 0.690, respectively, and the combined AUC was 0.843. A coding–noncoding co-expression (CNC) network was constructed based on Pearson’s correlation coefficient. A specific lncRNA–miRNA–mRNA regulatory network of ENST00000568297, ENST00000568243, and NR_046084 was also constructed. Functional annotation of the up- and down-regulated mRNAs was performed. Pathway analysis enriched IS-related pathways with mRNAs in the lncRNA–miRNA–mRNA regulatory network. Conclusion: LncRNA and mRNA expression profiles in human peripheral blood were altered after IS. ENST00000568297, ENST00000568243, and NR_046084 were identified as novel potential diagnostic biomarkers of IS. Analysis of the CNC network and lncRNA–miRNA–mRNA regulatory network suggested that lncRNAs may participate in IS pathophysiology by regulating pivotal miRNAs, mRNAs, or IS-related pathways.

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Identification of lncRNA–mRNA Regulatory Network Associated With Isolated Systolic Hypertension and Atherosclerotic Cerebral Infarction

10.21203/rs.3.rs-391143/v1 ◽

2021 ◽

Author(s):

jie Yang ◽

Yan-Nan Tao ◽

Fang-Xiao Hu ◽

Yong-Zhi Chen ◽

Xue-Song Yang ◽

...

Keyword(s):

Cerebral Infarction ◽

Regulatory Network ◽

Systolic Hypertension ◽

Expression Profiles ◽

Pearson Correlation ◽

Interaction Network ◽

Differentially Expressed ◽

Isolated Systolic Hypertension ◽

Hub Genes ◽

Qrt Pcr

Abstract Background: Increasing evidences uncover that lncRNAs play an important role in Isolated systolic hypertension (ISH). However, a systematic lncRNA-mRNA regulatory network is still absent in isolated systolic hypertension and atherosclerotic cerebral infarction patients (ISH & ACI).Aim:This research aims to establish a lncRNA-mRNA co-expression network in patients with ISH & ACI, to probe into the potential functions of lncRNA in those patients.Design and Setting:Expression profiles of lncRNA and mRNAs are collected and compared respectively from 8 patients with ISH and 8 patients with ISH & ACI by RNA-seq data.Methods: Differentially expressed lncRNAs and mRNAs were screened out via high-throughput sequencing in the plasma of ISH/ACI patients and control ISH patients. Then, a lncRNA-mRNA interaction network was built using the Pearson correlation coefficient by Cytoscape software. The expression levels of the hub genes and lncRNAs were verified by qRT-PCR in another 10 ISH/ACI patients and 10 control patients. Results: 2768 differentially expressed lncRNAs and 747 differentially expressed mRNAs were identified. 2 hub genes (CD226 and PARVB) and 11 lncRNAs were identified in the lncRNA-mRNA interaction network. qRT-PCR and cell assay results verified that lncRNAs ENST00000590604 and CD226 are highly expressed in patients of ISH & ACI. CD226 was associated with vascular endothelial cells growth and stability through platelet activation and focal adhesion pathway.Conclusion: We established a novel mRNA-lncRNA interaction network. lncRNAs ENST00000590604 and CD226 might be the potential biomarkers of ISH & ACI.

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Construction of a circRNA - Mediated ceRNA Network Reveals Novel Biomarkers for Aortic Dissection

10.21203/rs.3.rs-1059642/v1 ◽

2021 ◽

Author(s):

De-Bin Liu ◽

You-Fu He ◽

Gui-Jian Chen ◽

Hua Huang ◽

Xu-Ling Xie ◽

...

Keyword(s):

Aortic Dissection ◽

Regulatory Network ◽

Molecular Mechanisms ◽

Kegg Pathway ◽

Expression Profiles ◽

Differentially Expressed ◽

Receptor Interaction ◽

Qrt Pcr ◽

Cerna Network ◽

Arterial Blood

Abstract Background Aortic dissection (AD) is a rare and lethal disorder with its genetic basis remains largely unknown. Many studies have confirmed that circular RNAs (circRNAs) play important roles in various physiological and pathological processes. However, the roles of circRNAs in AD are still unclear and need further investigation. The present study aimed to elucidate the underlying molecular mechanisms of circRNAs regulation in aortic dissection based on the circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network. Methods Expression profiles of circRNAs (GSE97745), miRNAs (GSE92427), and mRNAs (GSE52093) were downloaded from Gene Expression Omnibus (GEO) databases, and the differentially expressed RNAs (DERNAs) were subsequently identified in AD by bioinformatics analysis. Further bioinformatics analyses, including circRNA-miRNA-mRNA ceRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, were used to predict the potential functions of circRNA-associated ceRNA regulatory network. RNA was isolated from human arterial blood samples after which quantitative real-time PCR (qRT-PCR) was performed to confirm the DERNAs. Results We identified 14 (5 up-regulated and 9 down-regulated) differentially expressed circRNAs (DEcircRNAs), 17 (8 up-regulated and 9 down-regulated) differentially expressed miRNAs (DEmiRNAs) and 527 (297 up-regulated and 230 down-regulated) differentially expressed mRNAs (DEmRNAs) when AD samples were compared with normal ascending aorta samples (adjusted P-value < 0.05 and | log2FC |> 1.0). KEGG pathway analysis indicated that DEmRNAs were related to focal adhesion and extracellular matrix (ECM) receptor interaction signaling pathways. Simultaneously, the present study successfully constructed a ceRNA regulatory network based on 1 circRNAs (hsa_circRNA_082317), 1 miRNAs (hsa-miR-149-3p) and 10 mRNAs (MLEC, ENTPD7, SLC16A3, SLC7A8, TBC1D16, PAQR4, MAPK13, PIK3R2, ITGA5, SERPINA1) in AD. Furthermore, qRT-PCR demonstrated that hsa_circRNA_082317 andα5 integrin (ITGA5) were significantly up-regulated in AD (n = 3), and hsa-miR-149-3p was dramatically down-regulated in AD (n = 3). The expression of hsa-miR-149-3p target mRNA, ITGA5, was positively modulated by hsa_circRNA_082317. Conclusion This is the first study to demonstrate the circRNA-associated ceRNA regulatory network is altered in AD, implying that circRNAs may play important roles in regulating the onset and progression of AD and thus may serve as potential biomarkers for the diagnosis and treatment of AD.

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Identification of lncRNA–mRNA Regulatory Network Associated With Isolated Systolic Hypertension And Atherosclerotic Cerebral Infarction

10.21203/rs.3.rs-391143/v2 ◽

2021 ◽

Author(s):

Jie Yang ◽

Yan-Nan Tao ◽

Fang-Xiao Hu ◽

Yong-Zhi Chen ◽

Xue-Song Yang ◽

...

Keyword(s):

Cerebral Infarction ◽

Regulatory Network ◽

Systolic Hypertension ◽

Expression Profiles ◽

Pearson Correlation ◽

Interaction Network ◽

Differentially Expressed ◽

Isolated Systolic Hypertension ◽

Hub Genes ◽

Qrt Pcr

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Expression Profiles of Circular RNA in Human Atrial Fibrillation With Valvular Heart Diseases

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2020.597932 ◽

2020 ◽

Vol 7 ◽

Author(s):

Xiyu Zhu ◽

Xinlong Tang ◽

Hoshun Chong ◽

Hailong Cao ◽

Fudong Fan ◽

...

Keyword(s):

Regulatory Network ◽

Sanger Sequencing ◽

Kegg Pathway ◽

Heart Diseases ◽

Expression Profiles ◽

Signal Pathway ◽

Differentially Expressed ◽

Qrt Pcr ◽

Valvular Heart Diseases ◽

Human Atrial Fibrillation

Circular RNAs (circRNA) are involved in a variety of human heart diseases, however, circRNA expression profiles and circRNA-miRNA-mRNA regulatory network in human atrial fibrillation (AF) especially with valvular heart diseases (VHD) remain poorly understood. A high-throughput RNA sequencing was used to investigate the differentially expressed circRNAs in left atrial appendage from VHD patients with or without persistent AF. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the potential functions of the host genes of differentially expressed circRNA and their downstream targets. CircRNA–miRNA-mRNA regulatory network was constructed to identify mechanisms underlying circRNAs. qRT-PCR and sanger sequencing were further performed to validate the results. Compared with sinus rhythm (SR) patients, there were 3094 upregulated and 4472 downregulated circRNAs in AF patients respectively. The expression of 10 most differentially expressed circRNAs (circ 255-ITGA7, circ 418-KCNN2, circ 13913-MIB1, circ 44670-BARD1, circ 44782-LAMA2, circ 81906-RYR2, circ 35880-ANO5, circ 22249-TNNI3K, circ 3136-TNNI3K, circ 56186-TNNI3K) between SR and persistent AF patients were verified by qRT-PCR. In addition, specific back-splicing sites of these circRNAs was confirmed by sanger sequencing. GO and KEGG pathway analysis indicated that cAMP signal pathway and Wnt signal pathway might play important role in the development of AF in VHD patients, which might be affected by circRNAs. This study provided a preliminary landscape of circRNAs expression profiles which are involved in persistent AF due to VHD, and established the possibility for future related researches in this field.

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MiRNAs expression profiling of rat ovaries displaying PCOS with insulin resistance

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-020-05730-z ◽

2020 ◽

Vol 302 (5) ◽

pp. 1205-1213

Author(s):

Chunren Zhang ◽

Chuyi Yu ◽

Zengxian Lin ◽

Haixia Pan ◽

Kunyin Li ◽

...

Keyword(s):

Insulin Resistance ◽

Target Genes ◽

Kegg Pathway ◽

Polycystic Ovary ◽

Expression Profiles ◽

Differentially Expressed ◽

Real Time Quantitative Pcr ◽

Qrt Pcr ◽

Differentially Expressed Mirnas ◽

Pathway Analyses

Abstract Purpose The present study established microRNA (miRNA) expression profiles for rat ovaries displaying polycystic ovary syndrome (PCOS) with insulin resistance and explored the underlying biological functions of differentially expressed miRNAs. Methods A PCOS with insulin resistance rat model was created by administering letrozole and a high-fat diet. Total RNA was extracted from the ovaries of PCOS with insulin resistance rats and normal rats. Three ovaries from each group were used to identify differentially expressed miRNAs by deep sequencing. A hierarchical clustering heatmap and volcano plot were used to display the pattern of differentially expressed miRNAs. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the potential target genes of the differentially expressed miRNAs and identify their putative biological function. Nine of the differentially expressed miRNAs were selected for validation by Real-time Quantitative PCR (qRT-PCR). Results A total of 58 differentially expressed miRNAs were identified in the rat ovaries exhibiting PCOS with insulin resistance compared with control ovaries, including 23 miRNAs that were upregulated and 35 miRNAs that were downregulated. GO and KEGG pathway analyses revealed that the predicted target genes were related to metabolic processes, cellular processes, and metabolic pathways. Furthermore, qRT-PCR confirmed that miR-3585-5p and miR-30-5p were significantly upregulated and miR-146-5p was downregulated in the ovaries of PCOS with insulin resistance rats compared with the controls. Conclusion These results indicate that differentially expressed miRNAs in rat ovaries may be involved in the pathophysiology of insulin resistance in PCOS. Our study may be beneficial in establishing miRNAs as novel diagnostic and therapeutic biomarkers for insulin resistance in PCOS.

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Microarray Profiling of TGF-β1-Induced Long Non-Coding RNA Expression Patterns in Human Lung Bronchial Epithelial BEAS-2B Cells

Cellular Physiology and Biochemistry ◽

10.1159/000495052 ◽

2018 ◽

Vol 50 (6) ◽

pp. 2071-2085 ◽

Cited By ~ 4

Author(s):

Wentao Hu ◽

Weiwei Pei ◽

Lin Zhu ◽

Jing Nie ◽

Hailong Pei ◽

...

Keyword(s):

Human Lung ◽

Expression Patterns ◽

Differentially Expressed ◽

Bronchial Epithelial ◽

Qrt Pcr ◽

Microarray Profiling ◽

Underlying Mechanisms ◽

Pathway Analyses ◽

Trans Regulation ◽

Tgf Β1

Background/Aims: TGF-β1 mediated radiation-induced bystander effects (RIBE) have been linked with malignant transformation and tumorigenesis. However, the underlying mechanisms are not fully understood. Methods: To reveal new molecules of regulatory functions in this process, lncRNA microarray was performed to profile both lncRNA and mRNA expression patterns in human lung bronchial epithelial BEAS-2B cells treated with TGF-β1 at a concentration measured in the medium conditioned by directly irradiated BEAS-2B cells. The potential functions of the differentially expressed lncRNAs were predicted by GO and KEGG pathway analyses of their co-expressed mRNAs. Cis- and trans-regulation of the lncRNAs were analyzed and the interaction networks were constructed using Cytoscape. qRT-PCR was conducted to validate the results of microarray profiling. CCK-8 assay was employed for functional validation of 3 identified lncRNAs. Results: 224 lncRNAs were found to be dysregulated, among which 6 lncRNAs were chosen for expression validation by qRT-PCR assay. Pathway analyses showed that differentially expressed lncRNAs are highly correlated with cell proliferation, transformation, migration, etc. Trans-regulation analyses showed that the differentially expressed lncRNAs most likely participate in the pathways regulated by four transcriptional factors, FOS, STAT3, RAD21 and E2F1, which have been identified to be involved in the modulation of oncogenic transformation, cell cycle progression, genomic instability, etc. lnc-THEMIS-2 and lnc-ITGB6-4, predicted to be regulated by STAT3 and E2F1 respectively, were found to rescue the decrease of cell viability induced by TGF-β1 treatment. Conclusion: Our findings suggest that the differentially expressed lncRNAs induced by TGF-β1 play crucial roles in the oncogenic transformation and tumorigenesis, which provide a better understanding of the underlying mechanisms related to tumorigensis induced by LD/LDR radiations.

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CircRNA-miRNA-mRNA Regulatory Network in Colorectal Cancer

10.21203/rs.3.rs-829473/v1 ◽

2021 ◽

Author(s):

Liyuan Liu ◽

Shan Wu ◽

Dan Jiang ◽

Yuliang Qu ◽

Hongxia Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Regulatory Network ◽

Research Direction ◽

Differentially Expressed ◽

Circular Rnas ◽

Hub Genes ◽

Protein Protein Interaction ◽

Qrt Pcr ◽

Cancer Tissues ◽

Chip Analysis

Abstract Background: Abnormal expression of Circular RNAs (circRNAs) occurs in the occurrence and progression of colorectal cancer (CRC) and plays an important role in the pathogenesis of tumors. We combined bioinformatics and laboratory-validated methods to search for key circRNAs and possible potential mechanisms. Methods: Colorectal cancer tissues and normal paracancerous tissues were detected by microarray analysis and qRT-PCR validation, and differentially expressed circRNAs were screened and identified. The circRNA-miRNA-mRNA regulatory network (cirReNET) was constructed, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to ascertain the functions of circRNAs in CRCs. In addition, a protein-protein interaction (PPI) network of hub genes which acquired by string and plugin app CytoHubba in cytoscape was established. Validation of expression of hub genes was identified by GEPIA database. Results: 564 differentially expressed circRNAs which include 207 up-regulated and 357 down-regulated circRNAs were detected. The top 3 up-regulated circRNAs (hsa_circRNA_100833, hsa_circRNA_103828, hsa_circRNA_103831) and the top 3 down-regulated circRNAs (hsa_circRNA_103752, hsa_circRNA_071106, hsa_circRNA_102293) in chip analysis were chosen to be verified in 33 pairs of CRCs by qRT-PCR. The cirReNET include of 6 circRNAs, 19 miRNAs and 210 mRNA. And the targeted mRNAs were associated with cellular metabolic process, cell cycle and glandular epithelial cell differentiation and so on. 12 and 10 target hub genes were shown separately in upregulated circRNA-downregulated miRNA-upregulated mRNA (UcDiUm-RNA) group and downregulated circRNA-upregulated miRNA-downregulated mRNA (DcUiDm-RNA) group. Finally, we may have predicted and discovered several critical circRNA-miRNA-mRNA regulatory axes (cirReAXEs) which may play important roles in colorectal cancer. Conclusion: We constructed a cirReNET including 6 candidate circRNAs, which were crucial in CRCs, may become potential diagnostic markers and predictive indicators of CRCs, and we may provide a research direction for the pathogenesis of colorectal cancer.

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Identification of LOC338963 and AP3B2 as Potential Biomarkers for Lambert-Eaton Myasthenic Syndrome

10.21203/rs.3.rs-332560/v1 ◽

2021 ◽

Author(s):

Fei Yang ◽

Feng Jing ◽

Yang Li ◽

Shanshan Kong ◽

Shimin Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Expression Profiles ◽

Small Cell ◽

Differentially Expressed ◽

Healthy Controls ◽

Small Cell Lung ◽

Qrt Pcr ◽

Myasthenic Syndrome

Abstract Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder associated with muscle weakness and small-cell lung cancer. Here, we used microarray analysis to identify long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) that might serve as biomarkers for LEMS.Methods: Plasma lncRNA and mRNA expression profiles of three patients with paraneoplastic LEMS and three healthy controls were analyzed using Arraystar Human lncRNA Microarray v4.0. Differentially expressed lncRNAs and adjacent mRNAs were analyzed jointly, and candidates were verified in individual samples by quantitative real-time polymerase chain reaction (qRT-PCR). The identified lncRNAs and mRNAs were evaluated in nine patients with paraneoplastic LEMS, eight patients with non-tumor LEMS, and four patients with small cell lung cancer (SCLC). Results: A total of 320 lncRNAs were differentially expressed in patients with paraneoplastic LEMS compared to healthy controls (fold change >1.5, P < 0.05), and nine were further evaluated. One of the identified lncRNAS, LOC338963 (NR_031439), is known to regulated the expression of the mRNA AP3B2, and both were upregulated more than 2-fold in patients with paraneoplastic LEMS compared to healthy controls. Furthermore, qRT-PCR analysis revealed significant upregulation of LOC338963 (NR_031439) and AP3B2 expression in patients with paraneoplastic LEMS compared to those with either non-tumor LEMS (2.37- and 5.06-fold, respectively) or SCLC (4.36- and 14.97-fold, respectively).Conclusions: Plasma LOC338963 (NR_031439) and AP3B2 were found to be upregulated in LEMS and might be used as diagnostic biomarkers for this disease.

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Abstract WP120: MicroRNA Expression in Patients With Acute Ischemic Stroke

Stroke ◽

10.1161/str.48.suppl_1.wp120 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Janhavi M Modak ◽

Meaghan A Roy-O’Reilly ◽

Sarah E Conway ◽

Liang Zhu ◽

Louise D McCullough

Keyword(s):

Ischemic Stroke ◽

Differential Expression ◽

Expression Profiles ◽

Outpatient Setting ◽

Microrna Expression ◽

Neurological Deficits ◽

Stroke Patients ◽

Significant Differential Expression ◽

Blood Samples ◽

Mrna Targets

Background and Purpose: MicroRNAs (miRNAs) are a class of endogenous small non-coding ribonucleic acids that regulate gene expression and can impact cellular function by suppressing or activating downstream mRNA targets. Pre-clinical studies in animal models of stroke have demonstrated specific changes in miRNA expression profiles after ischemic stroke. Methods: Patients admitted to Hartford Hospital from January 2011 - March 2014 were considered for this study. Blood samples were collected within 24 hours of stroke presentation. miRNA profiles from peripheral blood samples of ischemic stroke patients were compared to controls. Patients with acute middle cerebral artery (MCA) cardioembolic strokes (based on TOAST criteria) were included (n=16). Blood collected from patients with no acute neurological deficits in an outpatient setting served as controls (n=8). Individuals with a history of active cancer, neoplastic brain lesions or traumatic brain injury were excluded. Based on literature review, 173 miRNAs were selected to assess for differential expression between cases and controls. miRNA profiling was conducted at Exiqon Services, Denmark, using miRCURY LNA™ microRNA Array. Statistical analysis was performed using SAS. Results: In patients with acute ischemic strokes, a statistically significant differential expression was observed in 14 miRNAs as compared to controls. MicroRNAs miR-1273e, miR-5187-3p were found to be downregulated in stroke patients (p=0.01). Other miRNAs showing a significant downregulation included let 7e-5p (p=0.03); miR-4709-3p, miR-4756-3p, miR-5584-3p, miR-647 (p=0.02); miR-4742-3p (p=0.03); miR-4764-5p, miR-4531 and miR-2116-5p (p=0.04). MicroRNAs miR-664a-3p (p=0.02), miR-943 (p=0.04) and miR-145-5p (p=0.03) were significantly upregulated. Differential expression in males and females was not observed. Conclusion: Ischemic stroke patients show a differential microRNA expression profile as compared to controls. Further studies can help identify microRNA signatures as well as the downstream targets involved in the ischemic stroke molecular cascade.

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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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