An Integrative Data Mining for the Identification and Validation of Oncogenic Biomarkers in Pancreatic Carcinoma

Abstract Background: Pancreatic carcinoma (PC) is a severe disease associated with high mortality. Although strategies for cancer therapy made great progress, outcomes of pancreatic ductal adenocarcinoma patients remain extremely poor. Therefore, it is urgent to find novel biomarkers and therapeutic targets to improve outcomes of patients. Methods: To identify general applicable targets for early diagnosis and therapy, we selected related microarray data which including three mRNA microarray datasets GSE62165, GSE15471, GSE32676 and two miRNA datasets GSE24279, GSE32678, and combinative analysis was performed by GEO2R. Functional and pathway enrichment analysis were performed using the DAVID database. MiRTarBase, miRWalk, Diana Tools and TBtools were used to get keys. TCGA database, HPA database and western blot experiments were used to verify diagnostic and prognostic value of key genes.Results: By integrating mRNA and miRNA expression profiles, we identified 114 differentially expressed genes (DEGs) and 114 differentially expressed miRNAs (DEMs), respectively. Furthermore, three overlapping key genes, RUNX2, LAMC2 and FBXO32, were found by compared with DEMs target genes and DEGs. In detail, deregulation of 8 key miRNAs were closely related to poor outcomes and participated in crucial genes regulation which may contribute to build a miRNA biomarker panel for prognosis. Moreover, we confirmed that RUNX2 showed a potential property for distinguishing PC and normal people. We also demonstrated that aberrant over-expression of LAMC2 was associated with poor prognosis of PC patients as well as human tumor status and subtypes. The protein levels of RUNX2 and LAMC2 in PC patients were further verified by IHC from Human Protein Atlas and western blot experiments. Conclusions: In summary, our current study identified that RUNX2 and LAMC2 may be promising targets for early diagnosis and therapy of PC patients.

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Effect of miR-27b-5p on apoptosis of human vascular endothelial cells induced by simulated microgravity

APOPTOSIS ◽

10.1007/s10495-019-01580-6 ◽

2019 ◽

Vol 25 (1-2) ◽

pp. 73-91 ◽

Cited By ~ 1

Author(s):

Yi-Kai Pan ◽

Cheng-Fei Li ◽

Yuan Gao ◽

Yong-Chun Wang ◽

Xi-Qing Sun

Keyword(s):

Endothelial Cells ◽

Western Blot ◽

Target Gene ◽

Simulated Microgravity ◽

Target Genes ◽

Expression Profiles ◽

Differentially Expressed ◽

Luciferase Assay ◽

Qrt Pcr ◽

Differentially Expressed Mirnas

AbstractWeightlessness-induced cardiovascular dysfunction can lead to physiological and pathological consequences. It has been shown that spaceflight or simulated microgravity can alter expression profiles of some microRNAs (miRNAs). Here, we attempt to identify the role of miRNAs in human umbilical vein endothelial cells (HUVECs) apoptosis under simulated microgravity. RNA-sequencing and quantitative real-time PCR (qRT-PCR) assays were used to identify differentially expressed miRNAs in HUVECs under simulated microgravity. Then we obtained the target genes of these miRNAs through target analysis software. Moreover, GO and KEGG enrichment analysis were performed. The effects of these miRNAs on HUVECs apoptosis were evaluated by flow cytometry, Western blot and Hoechst staining. Furthermore, we obtained the target gene of miR-27b-5p by luciferase assay, qRT-PCR and Western blot. Finally, we investigated the relationship between this target gene and miR-27b-5p in HUVECs apoptosis under normal gravity or simulated microgravity. We found 29 differentially expressed miRNAs in HUVECs under simulated microgravity. Of them, the expressions of 3 miRNAs were validated by qRT-PCR. We demonstrated that miR-27b-5p affected HUVECs apoptosis by inhibiting zinc fingers and homeoboxes 1 (ZHX1). Our results reported here demonstrate for the first time that simulated microgravity can alter the expression of some miRNAs in HUVECs and miR-27b-5p may protect HUVECs from apoptosis under simulated microgravity by targeting ZHX1.

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Investigation of microRNA Expression Profiles Associated with Human Alcoholic Cardiomyopathy

Cardiology ◽

10.1159/000370028 ◽

2015 ◽

Vol 130 (4) ◽

pp. 223-233 ◽

Cited By ~ 15

Author(s):

Ling Jing ◽

Chengmei Jin ◽

Ying Lu ◽

Pingyan Huo ◽

Lijun Zhou ◽

...

Keyword(s):

Real Time ◽

Target Genes ◽

Inositol Phosphate ◽

Expression Profiles ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Rt Pcr ◽

Alcoholic Cardiomyopathy ◽

Differentially Expressed Mirnas ◽

Human Alcoholic

Objectives: We aimed to investigate the differentially expressed microRNAs (miRNAs) and their target genes in human alcoholic cardiomyopathy (ACM). Methods: The expression levels of plasma miRNAs of 78 male ACM patients and 78 healthy men were detected by using the 6th-generation miRCURY™ LNA array (v.16.0). The prediction analysis for microarrays (PAM) method was used to identify the differentially expressed miRNAs. Target genes of the identified differentially expressed miRNAs were predicted using TargetScan 5.2 and Miranda. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to perform functional annotation and pathway enrichment analysis of target genes respectively, followed by real-time RT-PCR analysis to validate the expression changes of miRNAs. Results: Twenty-one differentially expressed miRNAs were identified. Nine differentially expressed miRNAs (hsa-miR-506, hsa-miR-1285, hsa-miR-512-3P, hsa-miR-138, hsa-miR-485-5P, hsa-miR-4262, hsa-miR-548c-3P, has-miR-548a-5P and kshv-miR-K12-1), involved in multiple functions and pathways, were selected for real-time RT-PCR confirmation. Moreover, two significantly important subpathways (neurotrophin signaling pathway and inositol phosphate metabolism) were predicted. Conclusion: The screened differentially expressed miRNAs may be involved in the development of ACM. Specific miRNAs, such as miR-138, may be considered as a new target for the early diagnosis and treatment of human ACM.

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Comprehensive bioinformatics analysis of mRNA expression profiles and identification of a miRNA–mRNA network associated with lupus nephritis

Lupus ◽

10.1177/0961203320925155 ◽

2020 ◽

Vol 29 (8) ◽

pp. 854-861

Author(s):

Jianbo Song ◽

Liqin Zhao ◽

Yuanping Li

Keyword(s):

Lupus Nephritis ◽

Mrna Expression ◽

Lupus Erythematosus ◽

Target Genes ◽

Expression Profiles ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Ppi Network

Objective Lupus nephritis (LN) is one of the serious complications of systemic lupus erythematosus. The aim of this study was to identify core genes and pathways involved in the pathogenesis of LN. Methods We screened differentially expressed genes (DEGs) in LN patients using mRNA expression profile data from the Gene Expression Omnibus. The functional and pathway enrichment analysis of DEGs was performed utilizing the Database for annotation, Visualization and Integrated Discovery. Target genes with differentially expressed miRNAs (DEMIs) were predicted using the miRTarBase database, and the intersection between these target genes and DEGs was selected to be studied further. Results In total, 107 common DEGs (CDEGs) were identified from the Tub_LN group and Glom_LN group, and 66 DEMIs were identified. Fifty-three hub genes and two significant modules were identified from the protein–protein interaction (PPI) network, and a miRNA–mRNA network was constructed. The CDEGs, module genes in the PPI network and genes intersecting with the CDEGs and target genes of DEMIs were all associated with the PI3K-Akt signalling pathway. Conclusion In summary, this study reveals some crucial genes and pathways potentially involving in the pathogenesis of LN. These findings provide a new insight for the research and treatment of LN.

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Expression Profiling of Cellular MicroRNA in Asymptomatic HBsAg Carriers and Chronic Hepatitis B Patients

BioMed Research International ◽

10.1155/2017/6484835 ◽

2017 ◽

Vol 2017 ◽

pp. 1-17 ◽

Cited By ~ 7

Author(s):

Xianliang Hou ◽

Yan Liang ◽

Jianing Chen ◽

Yingfeng Wei ◽

Ping Zeng ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Signaling Pathway ◽

Chronic Hepatitis B ◽

Target Genes ◽

Mononuclear Cells ◽

Expression Profiles ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Peripheral Blood Mononuclear

Background. MicroRNAs (miRNAs) may serve as potential molecular markers to predict liver injury resulting from chronic hepatitis B (CHB). In the present study, we want to study the expression profile and clinical significance of miRNAs at different stages of CHB virus infection. Methods. Using miRNA microarray, we investigated the global expression profiles of cellular miRNA in asymptomatic hepatitis B antigen carriers (ASCs) and CHB patients, compared with healthy controls (HCs). Results. We identified 79 and 203 differentially expressed miRNAs in the peripheral blood mononuclear cells of ASCs and CHB patients compared to HCs, respectively. Some of these miRNAs were common to ASCs and CHB patients, but another set of miRNAs that showed differential expression between ASCs and CHB patients was also identified. Gene ontology and pathway enrichment analysis showed that the target genes of the identified miRNAs played a role in important biological functions, such as learning or memory, cell-cell adherens junction, ion channel inhibitor activity, TGF-beta signaling pathway, and p53 signaling pathway. Conclusion. We identified some significant differentially expressed miRNA in different phases of HBV infection, which might serve as biomarkers or therapeutic targets in the future.

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Genome-wide transcriptome profiling uncovers differential miRNAs and lncRNAs in ovaries of Hu sheep at different developmental stages

Scientific Reports ◽

10.1038/s41598-021-85245-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Samina Shabbir ◽

Prerona Boruah ◽

Lingli Xie ◽

Muhammad Fakhar-e-Alam Kulyar ◽

Mohsin Nawaz ◽

...

Keyword(s):

Target Genes ◽

Expression Profiles ◽

Ovarian Follicle ◽

Follicular Development ◽

Differentially Expressed ◽

Ovary Development ◽

Estrogen Metabolism ◽

Genome Wide ◽

Micro Rnas ◽

Hu Sheep

AbstractOvary development is an important determinant of the procreative capacity of female animals. Here, we performed genome-wide sequencing of long non-coding RNAs (lncRNAs) and mRNAs on ovaries of 1, 3 and 8 months old Hu sheep to assess their expression profiles and roles in ovarian development. We identified 37,309 lncRNAs, 45,404 messenger RNAs (mRNAs) and 330 novel micro RNAs (miRNAs) from the transcriptomic analysis. Six thousand, seven hundred and sixteen (6716) mRNAs and 1972 lncRNAs were significantly and differentially expressed in ovaries of 1 month and 3 months old Hu sheep (H1 vs H3). These mRNAs and target genes of lncRNAs were primarily enriched in the TGF-β and PI3K-Akt signalling pathways which are closely associated with ovarian follicular development and steroid hormone biosynthesis regulation. We identified MSTRG.162061.1, MSTRG.222844.7, MSTRG.335777.1, MSTRG.334059.16, MSTRG.188947.6 and MSTRG.24344.3 as vital genes in ovary development by regulating CTNNB1, CCNA2, CDK2, CDC20, CDK1 and EGFR expressions. A total of 2903 mRNAs and 636 lncRNAs were differentially expressed in 3 and 8 months old ovaries of Hu sheep (H3 vs H8); and were predominantly enriched in PI3K-Akt, progesterone-mediated oocyte maturation, estrogen metabolism, ovulation from the ovarian follicle and oogenesis pathways. These lncRNAs were also found to regulate FGF7, PRLR, PTK2, AMH and INHBA expressions during follicular development. Our result indicates the identified genes participate in the development of the final stages of follicles and ovary development in Hu sheep.

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Bioinformatics-Based Study to Investigate Potential Differentially Expressed Genes and miRNAs in Hashimoto’s Thyroiditis

10.21203/rs.3.rs-1023446/v1 ◽

2021 ◽

Author(s):

Li Guoquan ◽

Du Junwei ◽

He Qi ◽

Fu Xinghao ◽

Ji Feihong ◽

...

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Inflammatory Responses ◽

Expression Profiles ◽

Treatment Options ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Chronic Lymphocytic Thyroiditis ◽

Hub Genes

Abstract BackgroundHashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a common autoimmune disease, which mainly occurs in women. The early manifestation was hyperthyroidism, however, hypothyroidism may occur if HT was not controlled for a long time. Numerous studies have shown that multiple factors, including genetic, environmental, and autoimmune factors, were involved in the pathogenesis of the disease, but the exact mechanisms were not yet clear. The aim of this study was to identify differentially expressed genes (DEGs) by comprehensive analysis and to provide specific insights into HT. MethodsTwo gene expression profiles (GSE6339, GSE138198) about HT were downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were assessed between the HT and normal groups using the GEO2R. The DEGs were then sent to the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were discovered using Cytoscape and CytoHubba. Finally, NetworkAnalyst was utilized to create the hub genes' targeted microRNAs (miRNAs). ResultsA total of 62 DEGs were discovered, including 60 up-regulated and 2 down-regulated DEGs. The signaling pathways were mainly engaged in cytokine interaction and cytotoxicity, and the DEGs were mostly enriched in immunological and inflammatory responses. IL2RA, CXCL9, IL10RA, CCL3, CCL4, CCL2, STAT1, CD4, CSF1R, and ITGAX were chosen as hub genes based on the results of the protein-protein interaction (PPI) network and CytoHubba. Five miRNAs, including mir-24-3p, mir-223-3p, mir-155-5p, mir-34a-5p, mir-26b-5p, and mir-6499-3p, were suggested as likely important miRNAs in HT. ConclusionsThese hub genes, pathways and miRNAs contribute to a better understanding of the pathophysiology of HT and offer potential treatment options for HT.

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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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Identification of Exogenous Nitric Oxide-Responsive miRNAs from Alfalfa (Medicago sativa L.) under Drought Stress by High-Throughput Sequencing

Genes ◽

10.3390/genes11010030 ◽

2019 ◽

Vol 11 (1) ◽

pp. 30

Author(s):

Yaodong Zhao ◽

Wenjing Ma ◽

Xiaohong Wei ◽

Yu Long ◽

Ying Zhao ◽

...

Keyword(s):

Nitric Oxide ◽

Drought Stress ◽

Medicago Sativa ◽

High Throughput ◽

Drought Resistance ◽

High Throughput Sequencing ◽

Target Genes ◽

Expression Profiles ◽

Differentially Expressed ◽

Medicago Sativa L

Alfalfa (Medicago sativa L.) is a high quality leguminous forage. Drought stress is one of the main factors that restrict the development of the alfalfa industry. High-throughput sequencing was used to analyze the microRNA (miRNA) profiles of alfalfa plants treated with CK (normal water), PEG (polyethylene glycol-6000; drought stress), and PEG + SNP (sodium nitroprusside; nitric oxide (NO) sprayed externally under drought stress). We identified 90 known miRNAs belonging to 46 families and predicted 177 new miRNAs. Real-time quantitative fluorescent PCR (qRT-PCR) was used to validate high-throughput expression analysis data. A total of 32 (14 known miRNAs and 18 new miRNAs) and 55 (24 known miRNAs and 31 new miRNAs) differentially expressed miRNAs were identified in PEG and PEG + SNP samples. This suggested that exogenous NO can induce more new miRNAs. The differentially expressed miRNA maturation sequences in the two treatment groups were targeted by 86 and 157 potential target genes, separately. The function of target genes was annotated by gene ontology (GO) enrichment and kyoto encyclopedia of genes and genomes (KEGG) analysis. The expression profiles of nine selected miRNAs and their target genes verified that their expression patterns were opposite. This study has documented that analysis of miRNA under PEG and PEG + SNP conditions provides important insights into the improvement of drought resistance of alfalfa by exogenous NO at the molecular level. This has important scientific value and practical significance for the improvement of plant drought resistance by exogenous NO.

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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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RNA-Seq Reveals the Expression Profiles of Long Non-Coding RNAs in Lactating Mammary Gland from Two Sheep Breeds with Divergent Milk Phenotype

Animals ◽

10.3390/ani10091565 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1565

Author(s):

Zhiyun Hao ◽

Yuzhu Luo ◽

Jiqing Wang ◽

Jiang Hu ◽

Xiu Liu ◽

...

Keyword(s):

Mammary Gland ◽

Signaling Pathway ◽

Target Genes ◽

Mammary Epithelial Cells ◽

Expression Profiles ◽

Wnt Signaling Pathway ◽

Mammary Epithelial ◽

Differentially Expressed ◽

Rna Seq ◽

Non Coding Rnas

Long non-coding RNAs (lncRNAs) are a kind of non-coding RNA with >200 nucleotides in length. Some lncRNAs have been proven to have clear regulatory functions in many biological processes of mammals. However, there have been no reports on the roles of lncRNAs in ovine mammary gland tissues. In the study, the expression profiles of lncRNAs were studied using RNA-Seq in mammary gland tissues from lactating Small-Tailed Han (STH) ewes and Gansu Alpine Merino (GAM) ewes with different milk yield and ingredients. A total of 1894 lncRNAs were found to be expressed. Compared with the GAM ewes, the expression levels of 31 lncRNAs were significantly up-regulated in the mammary gland tissues of STH ewes, while 37 lncRNAs were remarkably down-regulated. Gene Ontogeny (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the target genes of differentially expressed lncRNAs were enriched in the development and proliferation of mammary epithelial cells, morphogenesis of mammary gland, ErbB signaling pathway, and Wnt signaling pathway. Some miRNA sponges of differentially expressed lncRNAs, reported to be associated with lactation and mammary gland morphogenesis, were found in a lncRNA-miRNA network. This study reveals comprehensive lncRNAs expression profiles in ovine mammary gland tissues, thereby providing a further understanding of the functions of lncRNAs in the lactation and mammary gland development of sheep.

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