Comprehensive analysis of Helicobacter pylori infection-associated diseases based on miRNA-mRNA interaction network

AbstractHelicobacter pylori (H. pylori) infection remains a cause of significant morbidity and mortality worldwide. Comprehensive understanding of the pathogenic mechanism of H. pylori and its interaction with host will contribute to developing novel prophylactical and therapeutical strategies. Here, we first determined microRNA (miRNA) levels in H. pylori-infected patients with gastritis, duodenal ulcer, gastric cancer or mucosa-associated lymphoid tissue lymphoma using miRNA data sets. Thirty-four differentially expressed miRNAs were identified and functional enrichment analysis of those miRNA target genes revealed that H. pylori infection were strongly associated with pathway in cancer and regulation of mRNA synthesis. Using disease connectivity analysis of 28 hub genes, we found that H. pylori may increase the risk of many extragastric diseases (e.g. cardiovascular disease, hemic and lymphatic diseases and nervous system disease). Altogether, our integrated analysis provided a new method to predict pathogen–human disease connectivity based on miRNA-mRNA interaction network and indicated anti-H. pylori therapy as an effective means of human diseases prevention.

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System Analysis of MIRNAs in Maize Internode Elongation

Biomolecules ◽

10.3390/biom9090417 ◽

2019 ◽

Vol 9 (9) ◽

pp. 417

Author(s):

Chuanxi Peng ◽

Xing Wang ◽

Tianyu Feng ◽

Rui He ◽

Mingcai Zhang ◽

...

Keyword(s):

Target Genes ◽

System Analysis ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Differentially Expressed ◽

Internode Elongation ◽

Differentially Expressed Mirnas ◽

Post Transcriptional Regulation

MicroRNAs (miRNAs), the post-transcriptional gene regulators, are known to play an important role in plant development. The identification of differentially expressed miRNAs could better help us understand the post-transcriptional regulation that occurs during maize internode elongation. Accordingly, we compared the expression of MIRNAs between fixed internode and elongation internode samples and classified six differentially expressed MIRNAs as internode elongation-responsive miRNAs including zma-MIR160c, zma-MIR164b, zma-MIR164c, zma-MIR168a, zma-MIR396f, and zma-MIR398b, which target mRNAs supported by transcriptome sequencing. Functional enrichment analysis for predictive target genes showed that these miRNAs were involved in the development of internode elongation by regulating the genes respond to hormone signaling. To further reveal how miRNA affects internode elongation by affecting target genes, the miRNA–mRNA–PPI (protein and protein interaction) network was constructed to summarize the interaction of miRNAs and these target genes. Our results indicate that miRNAs regulate internode elongation in maize by targeting genes related to cell expansion, cell wall synthesis, transcription, and regulatory factors.

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Integrated Analysis of lncRNA and mRNA Reveals Novel Insights into Wool Bending in Zhongwei Goat

Animals ◽

10.3390/ani11113326 ◽

2021 ◽

Vol 11 (11) ◽

pp. 3326

Author(s):

Xiaobo Li ◽

Zhanfa Liu ◽

Shaohui Ye ◽

Yue Liu ◽

Qian Chen ◽

...

Keyword(s):

Signaling Pathway ◽

Target Genes ◽

Economic Value ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Hair Follicles ◽

Functional Enrichment ◽

Integrated Analysis ◽

Rna Seq ◽

Camp Signaling Pathway

Chinese Zhongwei goat is a rare and precious fur breed as its lamb fur is a well-known fur product. Wool bending of lamb fur of the Zhongwei goat is its most striking feature. However, the curvature of the wool decreases gradually with growth, which significantly affects its quality and economic value. The mechanism regulating the phenotypic changes of hair bending is still unclear. In the present study, the skin tissues of Zhongwei goats at 45 days (curving wool) and 108 days (slight-curving wool) after birth were taken as the research objects, and the expression profiling of long non-coding RNAs (lncRNAs) and mRNAs were analyzed based on the Ribo Zero RNA sequencing (RNA-seq) method. In total, 46,013 mRNAs and 13,549 lncRNAs were identified, of which 352 were differentially expressed mRNAs and 60 were. lncRNAs. Functional enrichment analysis of the target genes of lncRNAs were mainly enriched in PI3K-Akt, Arachidonic acid metabolic, cAMP, Wnt, and other signaling pathways. The qRT-PCR results of eight selected lncRNAs and target genes were consistent with the sequencing result, which indicated our data were reliable. Through the analysis of the weighted gene co-expression network, 13 co-expression modules were identified. The turquoise module contained a large number of differential expressed lncRNAs, which were mainly enriched in the PI3K-Akt signaling pathway and cAMP signaling pathway. The predicted LOC102172600 and LOC102191729 might affect the development of hair follicles and the curvature of wool by regulating the target genes. Our study provides novel insights into the potential roles of lncRNAs in the regulation of wool bending. In addition, the study offers a theoretical basis for further study of goat wool growth, so as to be a guidance and reference for breeding and improvement in the future.

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Integrative Bioinformatics Analysis Identifies Noninvasive miRNA Biomarkers for Lung Cancer

10.1101/2020.12.31.20248963 ◽

2021 ◽

Author(s):

Andrew Gao

Keyword(s):

Lung Cancer ◽

Messenger Rna ◽

Target Genes ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Gene Expression Omnibus ◽

Functional Enrichment ◽

Nsclc Patients ◽

Prognostic Power

AbstractNon-small cell lung cancer (NSCLC), a subtype of lung cancer, affects millions of people. While chemotherapy and other treatments have improved, the 5 year survival rate of NSCLC patients is still only 21%. Early diagnosis is essential for increasing survival as treatments have higher effectiveness at earlier stages of NSCLC. Noninvasive blood-based liquid biopsy tests for NSCLC may be useful for diagnosis and prognosis. MicroRNA (miRNA) and messenger RNA present in blood can serve as biomarkers for such tests. The present study identified 13 miRNAs that are underexpressed in the tissue and blood of NSCLC patients using Gene Expression Omnibus data. Following Kaplan Meier analysis, miR-140-3p, miR-29c, and miR-199a were selected as candidate biomarkers and demonstrated statistically significant prognostic power. An ROC analysis of miR-140-3p expression between NSCLC patients and controls had an area under curve value of 0.85. Functional enrichment analysis of the miRNA target genes revealed several overrepresented pathways relevant to cancer. Eight target genes were hub genes of the protein protein interaction network and possessed significant prognostic power. A combination of IL6, SNAI1, and CDK6 achieved a hazard ratio of 1.4 with p < 0.001. These biomarkers are especially valuable because they can be identified in blood and reflect the tumor state. Since all miRNAs were underexpressed in both tissue and blood, detecting expression of a biomarker miRNA in blood provides information on its expression in tissue as well. These miRNAs may be useful biomarkers for NSCLC prognostic and diagnostic tests and should be further studied.

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Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative Respiratory Pathogens Predicts Possible Association with Lung Adenocarcinoma

Pathophysiology ◽

10.3390/pathophysiology28010003 ◽

2021 ◽

Vol 28 (1) ◽

pp. 20-33

Author(s):

Lydia-Eirini Giannakou ◽

Athanasios-Stefanos Giannopoulos ◽

Chrissi Hatzoglou ◽

Konstantinos I. Gourgoulianis ◽

Erasmia Rouka ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Cell Junctions ◽

Respiratory Pathogens ◽

Gram Negative ◽

Human Proteins ◽

Apoptotic Pathways

Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.

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Identification of Tumorigenic and Prognostic Biomarkers in Colorectal Cancer Based on microRNA Expression Profiles

BioMed Research International ◽

10.1155/2020/7136049 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yuntao Shi ◽

Yingying Zhuang ◽

Jialing Zhang ◽

Mengxue Chen ◽

Shangnong Wu

Keyword(s):

Target Genes ◽

Cox Regression ◽

Expression Profiles ◽

Survival Rates ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Risk Groups ◽

Normal Mucosa ◽

Microrna Expression ◽

Functional Enrichment

Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.

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miRNA Mediated Noise Making of 3′UTR Mutations in Cancer

Genes ◽

10.3390/genes9110545 ◽

2018 ◽

Vol 9 (11) ◽

pp. 545 ◽

Cited By ~ 5

Author(s):

Wei Wu ◽

Lingxiang Wu ◽

Mengyan Zhu ◽

Ziyu Wang ◽

Min Wu ◽

...

Keyword(s):

Somatic Mutations ◽

Target Genes ◽

Expression Profiles ◽

Tumor Development ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Messenger Rnas ◽

Cellular Functions ◽

Mrna Binding

Somatic mutations in 3′-untranslated regions (3′UTR) do not alter amino acids and are considered to be silent in cancers. We found that such mutations can promote tumor progression by altering microRNA (miRNA) targeting efficiency and consequently affecting miRNA–mRNA interactions. We identified 67,159 somatic mutations located in the 3′UTRs of messenger RNAs (mRNAs) which can alter miRNA–mRNA interactions (functional somatic mutations, funcMutations), and 69.3% of these funcMutations (the degree of energy change > 12 kcal/mol) were identified to significantly promote loss of miRNA-mRNA binding. By integrating mRNA expression profiles of 21 cancer types, we found that the expression of target genes was positively correlated with the loss of absolute affinity level and negatively correlated with the gain of absolute affinity level. Functional enrichment analysis revealed that genes carrying funcMutations were significantly enriched in the MAPK and WNT signaling pathways, and analysis of regulatory modules identified eighteen miRNA modules involved with similar cellular functions. Our findings elucidate a complex relationship between miRNA, mRNA, and mutations, and suggest that 3′UTR mutations may play an important role in tumor development.

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Demethylation alters transcriptome profiling of buds and leaves in ‘Kyoho’ grape

BMC Plant Biology ◽

10.1186/s12870-020-02754-0 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Haoran Jia ◽

Zibo Zhang ◽

Ehsan Sadeghnezhad ◽

Qianqian Pang ◽

Shangyun Li ◽

...

Keyword(s):

Gene Expression ◽

Regulatory Networks ◽

Epigenetic Modification ◽

Deep Understanding ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Glutathione Metabolism ◽

Endogenous Factors

Abstract Background Grape buds and leaves are directly associated with the physiology and metabolic activities of the plant, which is monitored by epigenetic modifications induced by environment and endogenous factors. Methylation is one of the epigenetic regulators that could be involved in DNA levels and affect gene expression in response to stimuli. Therefore, changes of gene expression profile in leaves and bud through inhibitors of DNA methylation provide a deep understanding of epigenetic effects in regulatory networks. Results In this study, we carried out a transcriptome analysis of ‘Kyoho’ buds and leaves under 5-azacytidine (5-azaC) exposure and screened a large number of differentially expressed genes (DEGs). GO and KEGG annotations showed that they are mainly involved in photosynthesis, flavonoid synthesis, glutathione metabolism, and other metabolic processes. Functional enrichment analysis also provided a holistic perspective on the transcriptome profile when 5-azaC bound to methyltransferase and induced demethylation. Enrichment analysis of transcription factors (TFs) also showed that the MYB, C2H2, and bHLH families are involved in the regulation of responsive genes under epigenetic changes. Furthermore, hormone-related genes have also undergone significant changes, especially gibberellin (GA) and abscisic acid (ABA)-related genes that responded to bud germination. We also used protein-protein interaction network to determine hub proteins in response to demethylation. Conclusions These findings provide new insights into the establishment of molecular regulatory networks according to how methylation as an epigenetic modification alters transcriptome patterns in bud and leaves of grape.

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3131 ONCOSTREAMS: NOVEL DYNAMICS PATHOLOGICAL MULTICELLULAR STRUCTURES INVOLVED IN GLIOBLATOMA GROWTH AND INVASION

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.253 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 111-111 ◽

Cited By ~ 2

Author(s):

Andrea Comba ◽

Patrick Dunn ◽

Anna E Argento ◽

Padma Kadiyala ◽

Sebastien Motsch ◽

...

Keyword(s):

Extracellular Matrix ◽

Target Genes ◽

Collective Motion ◽

Malignant Tumors ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Genetically Engineered ◽

Functional Enrichment ◽

Low Grade ◽

Normal Brain

OBJECTIVES/SPECIFIC AIMS: Oncostreams represent a novel growth pattern of GBM. In this study we uncovered the cellular and molecular mechanism that regulates the oncostreams function in GBM growth and invasion. METHODS/STUDY POPULATION: We studied oncostreams organization and function using genetically engineered mouse gliomas models (GEMM), mouse primary patient derived GBM model and human glioma biopsies. We evaluated the molecular landscape of oncostreams by laser capture microdissection (LCM) followed by RNA-Sequencing and bioinformatics analysis. RESULTS/ANTICIPATED RESULTS: Oncostreams are multicellular structures of 10-20 cells wide and 2-400 μm long. They are distributed throughout the tumors in mouse and human GBM. Oncostreams are heterogeneous structures positive for GFAP, Nestin, Olig2 and Iba1 cells and negative for Neurofilament. Using GEMM we found a negative correlation between oncostream density and animal survival. Moreover, examination of patient’s glioma biopsies evidenced that oncostreams are present in high grade but no in low grade gliomas. This suggests that oncostreams may play a role in tumor malignancy. Our data also indicated that oncostreams aid local invasion of normal brain. Transcriptome analysis of oncostreams revealed 43 differentially expressed (DE) genes. Functional enrichment analysis of DE genes showed that “collagen catabolic processes”, “positive regulation of cell migration”, and “extracellular matrix organization” were the most over-represented GO biological process. Network analysis indicated that Col1a1, ACTA2, MMP9 and MMP10 are primary target genes. These genes were also overexpressed in more malignant tumors (WT-IDH) compared to the less malignant (IDH1- R132H) tumors. Confocal time lapse imagining of 3D tumor slices demonstrated that oncostreams display a collective motion pattern within gliomas that has not been seen before. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, oncostreams are anatomically and molecularly distinctive, regulate glioma growth and invasion, display collective motion and are regulated by the extracellular matrix. We propose oncostreams as novel pathological markers valuable for diagnosis, prognosis and designing therapeutics for GBM patients.

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Downregulation of miRNA-205 Expression and Biological Mechanism in Prostate Cancer Tumorigenesis and Bone Metastasis

BioMed Research International ◽

10.1155/2020/6037434 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Yu Sun ◽

Sheng-Hua Li ◽

Ji-Wen Cheng ◽

Gang Chen ◽

Zhi-Guang Huang ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Protein Level ◽

Target Genes ◽

Mrna Level ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Forest Plot ◽

Biological Mechanism

Background. The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. Materials and Methods. The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. Results. The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. Conclusion. miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.

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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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