Identification of key molecules in recurrent miscarriage based on bioinformatics analysis

Background: Recurrent miscarriage (RM) affects 1% to 5% of couples, and the mechanisms still stay unclear. In this study, we explored the underlying molecular mechanism and potential molecular biomarkers of RM as well as constructed a miRNA-mRNA regulation network. Methods: The microarray datasets GSE73025 and GSE22490, which represent mRNA and miRNA profiles, respectively, were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) with p-value < 0.05 and fold-change > 2 were identified while the miRNAs with p-value < 0.05 and fold-change > 1.3 were considered as significant differentially expressed miRNAs (DEMs). Results: A total of 373 DEGs, including 218 up-regulated genes and 155 down-regulated genes, were identified, while 138 up-regulated and 68 down-regulated DEMs were screened out. After functional enrichment analysis, we found GO biological process (BP) terms significantly enriched in the Fc-gamma receptor signaling pathway involved in phagocytosis. Moreover, signaling pathway analyses indicated that the neurotrophin signaling pathway (hsa04722) was the top KEGG enrichment. 6 hub genes (FPR1, C5AR1, CCR1, ADCY7, CXCR2, NPY) were screened out to construct a complex regulation network in RM because they had the highest degree of affecting the network. Besides, we constructed miRNA-mRNA network between DEMs target genes and DEGs in RM, including hsa-miR-1297- KLHL24 and hsa-miR-548a-5p-KLHL24 pairs. Conclusions: In conclusion, the novel differentially expressed molecules in the present study could provide a new sight to explore the pathogenesis of RM as well as potential biomarkers and therapeutic targets for RM diagnosis and treatment.

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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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Identification of novel genes and pathways in carotid atheroma using integrated bioinformatic methods

Scientific Reports ◽

10.1038/srep18764 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 10

Author(s):

Wenqing Nai ◽

Diane Threapleton ◽

Jingbo Lu ◽

Kewei Zhang ◽

Hongyuan Wu ◽

...

Keyword(s):

Signaling Pathway ◽

Transforming Growth Factor ◽

Interaction Network ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Transforming Growth Factor Β ◽

Functional Enrichment ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Atheromatous Plaques

Abstract Atherosclerosis is the primary cause of cardiovascular events and its molecular mechanism urgently needs to be clarified. In our study, atheromatous plaques (ATH) and macroscopically intact tissue (MIT) sampled from 32 patients were compared and an integrated series of bioinformatic microarray analyses were used to identify altered genes and pathways. Our work showed 816 genes were differentially expressed between ATH and MIT, including 443 that were up-regulated and 373 that were down-regulated in ATH tissues. GO functional-enrichment analysis for differentially expressed genes (DEGs) indicated that genes related to the “immune response” and “muscle contraction” were altered in ATHs. KEGG pathway-enrichment analysis showed that up-regulated DEGs were significantly enriched in the “FcεRI-mediated signaling pathway”, while down-regulated genes were significantly enriched in the “transforming growth factor-β signaling pathway”. Protein-protein interaction network and module analysis demonstrated that VAV1, SYK, LYN and PTPN6 may play critical roles in the network. Additionally, similar observations were seen in a validation study where SYK, LYN and PTPN6 were markedly elevated in ATH. All in all, identification of these genes and pathways not only provides new insights into the pathogenesis of atherosclerosis, but may also aid in the development of prognostic and therapeutic biomarkers for advanced atheroma.

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Circular RNA screening identifies circMYLK4 as a regulator of fast/slow myofibers in porcine skeletal muscles

10.21203/rs.3.rs-62413/v1 ◽

2020 ◽

Author(s):

Haigang Cao ◽

Jieming Liu ◽

Tianning Du ◽

Yihao Liu ◽

Xiaoyu Zhang ◽

...

Keyword(s):

Muscle Development ◽

Target Genes ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Circular Rna ◽

Functional Enrichment ◽

Differentially Expressed ◽

Marker Genes ◽

Type Conversion ◽

Myofiber Type

Abstract Background: The myofiber type is related to the quality of meat; specifically, slow-oxidized myofiber helps to increase the tenderness and juiciness of meat. An increasing number of studies have shown that circRNAs play a key role in skeletal muscle development. However, the key circRNAs that regulate myofiber types and their roles are still poorly understood.Results: A total of 40757 circRNAs were identified from the longissimus dorsi (LD) and the soleus (Sol) muscles, of which 10388 were co-expressed in the two muscles. Further analysis found 181 differentially expressed circRNAs in the LD compared with Sol. Functional enrichment analysis showed that target genes of differentially expressed circRNA-sponge miRNAs were enriched in the AMPK, FoxO and PI3K-Akt signaling pathways. In addition, we focused on a novel circRNA—circMYLK4. CircMYLK4 significantly increased the mRNA and protein levels of slow muscle marker genes and caused the flesh to turn red.Conclusion: Our study laid an essential foundation for further research on circRNAs in myofiber type conversion and the achievement of higher meat quality.

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Integrated In-silico Analysis to Study the Role of microRNAs in the Detection of Chronic Kidney Diseases

Current Bioinformatics ◽

10.2174/1574893614666190923115032 ◽

2020 ◽

Vol 15 (2) ◽

pp. 144-154

Author(s):

Amina Khan ◽

Andleeb Zahra ◽

Sana Mumtaz ◽

M. Qaiser Fatmi ◽

Muhammad J. Khan

Keyword(s):

Target Genes ◽

Kidney Development ◽

Kidney Diseases ◽

In Silico Analysis ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Renal Diseases ◽

P Value ◽

Chronic Kidney Diseases

Background: MicroRNAs (miRNAs) play an important role in the pathogenesis of various renal diseases, including Chronic Kidney Diseases (CKD). CKD refers to the gradual loss of kidney function with the declining Glomerular Functional Rate (GFR). Objective: This study focused on the regulatory mechanism of miRNA to control gene expression in CKD. Methods: In this context, two lists of Differentially Expressed Genes (DEGs) were obtained; one from the three selected experiments by setting a cutoff p-value of <0.05 (List A), and one from a list of target genes of miRNAs (List B). Both lists were then compared to get a common dataset of 33 miRNAs, each had a set of DEGs i.e. both up-regulated and down-regulated genes (List C). These data were subjected to functional enrichment analysis, network illustration, and gene homology studies. Results: This study confirmed the active participation of various miRNAs i.e. hsa -miR-15a-5p, hsa-miR-195-5p, hsa-miR-365-3p, hsa-miR-30a-5p, hsa-miR-124-3p, hsa-miR-200b-3p, and hsamiR- 429 in the dysregulation of genes involved in kidney development and function. Integrated analyses depicted that miRNAs modulated renal development, homeostasis, various metabolic processes, immune responses, and ion transport activities. Furthermore, homology studies of miRNA-mRNA hybrid highlighted the effect of partial complementary binding pattern on the regulation of genes by miRNA. Conclusion: The study highlighted the great values of miRNAs as biomarkers in kidney diseases. In addition, the need for further investigations on miRNA-based studies is also commended in the development of diagnostic, prognostic, and therapeutic tools for renal diseases.

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Integrative Analysis of four miRNA prognostic signatures of prostate cancer

10.21203/rs.3.rs-34448/v1 ◽

2020 ◽

Author(s):

Chen Chi ◽

Xianwu Chen ◽

Liping Yao ◽

Min Li ◽

Lanting Xiang ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Target Genes ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Differentially Expressed ◽

Protein Protein Interaction ◽

Cellular Processes ◽

Relationship Of

Abstract Background Prostate cancer (PCa) is the most common urological cancer among men, having a poor prognosis, which is hard to accurately evaluate based on the present methods. MicroRNAs (miRNAs), a class of internal non-coding small RNA, can involve in the regulation of tumor biological function. So far, many researchers have tried to explore the relationship of malignant progress of PCa with miRNA, while there are just limited studies conducting the comprehensive analysis of miRNA in PCa clinical significance. Methods The data of miRNA and mRNA expressions in PCa were downloaded from TCGA database, and were performed the overall survival (OS) analysis using Survival package of R software to harvest the differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs). The bioinformatics tools such as TargetScan, miRDB, and miRanda were also conducted to forecast the desired target genes related with prognostic DEMs. In addition, both GO and KEGG analyses were used to uncover the fundamental signaling pathways and cellular processes in PCa as well as the protein-protein interaction (PPI) network was constructed through STRING and Cytoscape software. Results Firstly, 4 DEMs (miR-19a-3p, miR-144-3p, miR-223-5p, and miR-483-3p) were found having significantly associated with overall survival in PCa. Based on the criteria with FDR < 0.05 and |log2FC| > 1, 33 genes were screened out as DEGs. Besides, the functional enrichment analysis revealed that these DEGs of 4 miRNAs may participate in cancer-related pathways like FoxO and PI3K-Akt signaling pathway. Lastly, the low expression of CD177 may be potentially associated with poor survival of patients in PCa. Conclusion This study systematically analyzed multiple PCa prognostic DEMs (miR-19a-3p, miR-144-3p, miR-223-5p, and miR-483-3p), and verified a novel DEG signature (CD177) that can be used to effectively assess the prognosis of PCa patients.

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Analysis of Serum miRNAs in Alzheimer’s Disease

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/15333175211021712 ◽

2021 ◽

Vol 36 ◽

pp. 153331752110217

Author(s):

Liu Lu ◽

Wen-Zhuo Dai ◽

Xi-Chen Zhu ◽

Tao Ma

Keyword(s):

Gene Expression ◽

Target Genes ◽

Enrichment Analysis ◽

Gene Interaction ◽

Functional Enrichment Analysis ◽

Gene Expression Omnibus ◽

Functional Enrichment ◽

Differentially Expressed ◽

Mitogen Activated Protein Kinase ◽

Regulatory Relationship

This paper was aimed to analyze the microRNA (miRNA) signatures in Alzheimer disease (AD) and find the significant expressions of miRNAs, their target genes, the functional enrichment analysis of the confirmed genes, and potential drug treatment. The miRNA expression information of the gene expression profile data was downloaded from the Gene Expression Omnibus database. The total data sample size is 1309, including 1021 AD samples and 288 normal samples. A total of 21 differentially expressed miRNAs were obtained, of which 16 (hsa-miR-6761-3p, hsa-miR-6747-3p, hsa-miR-6875-3p, hsa-miR-6754-3p, hsa-miR-6736-3p, hsa-miR-6762-3p, hsa-miR-6787-3p, hsa-miR-208a-5p, hsa-miR-6740-3p, hsa-miR-6778-3p, hsa-miR-595, hsa-miR-6753-3p, hsa-miR-4747-3p, hsa-miR-3646, hsa-miR-6716-3p and hsa-miR-4435) were up-regulated and 5 (hsa-miR-125a-3p, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-6131 and hsa-miR-125b-1-3p) were down-regulated in AD. A total of 6 miRNAs (hsa-miR-595, hsa-miR-3646, hsa-miR-4435 hsa-miR-125a-3p, hsa-miR-22-3p and hsa-miR-24-3p) and 78 miRNA-disease-related gene sub-networks were predicted, and 116 ceRNA regulatory relationship pairs, and the ceRNA regulatory network were obtained. The results of enrichment analysis suggested that the main target pathways of several miRNAs differentially expressed in AD were mitogen-activated protein kinase signal pathway. According to the prediction results of Drug-Gene Interaction database 2.0, we obtained 53 pairs of drug-gene interaction, including 7 genes (PTGS2, EGFR, CALM1, PDE4D, FGFR2, HMGCR, cdk6) and 53 drugs. We hope our results are helpful to find a viable way to prevent, delay the onset, diagnose, and treat AD.

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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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Circular RNA screening identifies circMYLK4 as a regulator of fast/slow myofibers in porcine skeletal muscles

10.21203/rs.3.rs-120895/v1 ◽

2020 ◽

Author(s):

Haigang Cao ◽

Jieming Liu ◽

Tianning Du ◽

Yihao Liu ◽

Xiaoyu Zhang ◽

...

Keyword(s):

Muscle Development ◽

Target Genes ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Circular Rna ◽

Functional Enrichment ◽

Differentially Expressed ◽

Marker Genes ◽

Type Conversion ◽

Myofiber Type

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Regulatory role of non-coding RNA in ginseng rusty root symptom tissue

Scientific Reports ◽

10.1038/s41598-021-88709-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xingbo Bian ◽

Pengcheng Yu ◽

Ling Dong ◽

Yan Zhao ◽

He Yang ◽

...

Keyword(s):

Fatty Acid ◽

Regulatory Networks ◽

Target Genes ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Differentially Expressed ◽

Circular Rnas ◽

Primary Metabolism ◽

Non Coding Rna

AbstractGinseng rusty root symptom (GRS) is one of the primary diseases of ginseng. It leads to a severe decline in the quality of ginseng and significantly affects the ginseng industry. The regulatory mechanism of non-coding RNA (ncRNA) remains unclear in the course of disease. This study explored the long ncRNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) in GRS tissues and healthy ginseng (HG) tissues and performed functional enrichment analysis of the screened differentially expressed ncRNAs. Considering the predictive and regulatory effects of ncRNAs on mRNAs, we integrated ncRNA and mRNA data to analyze and construct relevant regulatory networks. A total of 17,645 lncRNAs, 245 circRNAs, and 299 miRNAs were obtained from HG and GRS samples, and the obtained ncRNAs were characterized, including the classification of lncRNAs, length and distribution of circRNA, and the length and family affiliations of miRNAs. In the analysis of differentially expressed ncRNA target genes, we found that lncRNAs may be involved in the homeostatic process of ginseng tissues and that lncRNAs, circRNAs, and miRNAs are involved in fatty acid-related regulation, suggesting that alterations in fatty acid-related pathways may play a key role in GRS. Besides, differentially expressed ncRNAs play an essential role in regulating transcriptional translation processes, primary metabolism such as starch and sucrose, and secondary metabolism such as alkaloids in ginseng tissues. Finally, we integrated the correlations between ncRNAs and mRNAs, constructed corresponding interaction networks, and identified ncRNAs that may play critical roles in GRS. These results provide a basis for revealing GRS's molecular mechanism and enrich our understanding of ncRNAs in ginseng.

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Identification of Potential Target Genes in HER-2 Positive Breast Cancer by Bioinformatics Analysis.

10.21203/rs.3.rs-34161/v1 ◽

2020 ◽

Author(s):

Song Wang ◽

Yi Quan ◽

Hongying Lyu ◽

Jian Deng

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Signaling Pathway ◽

Target Genes ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Ppi Network ◽

Her 2 ◽

Positive Breast Cancer

Abstract Background: HER-2 positive breast cancer has a high risk of for relapse, metastasis and drug resistance, and is correlated with a poor prognosis. Thus, the study objective was to reveal target genes and key pathways in HER-2 subtype breast cancer. Methods: The gene expression dataset (GSE29431) was downloaded from the Gene Expression Omnibus database(GEO), and the differentially expressed genes (DEGs) were determined using LIMMA package in R software. Subsequently, Functional enrichment analysis were performed in ClusterProfiler package of R platform. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to construct a Protein-Protein Interaction (PPI) network of DEGs. Module analysis and target genes were identified by Cytoscape software. Further more, The influence of target genes on overall survival (OS) was assessed using the Kaplan-Meier plotter database.Results: The differential expression analysis revealed 96 genes were up-regulated while 407 genes were down-regulated in HER-2 positive breast cancer tissue compared to normal breast tissue. Functional enrichment analysis showed that the DEGs were mainly involved in regulation of lipid metabolic process, PPAR signaling pathway and PI3K-Akt signaling pathway. PPI network construction revealed a total of 199 nodes and 560 edges, and 12 target genes were identified by the highest value of degree. In addition, target genes were associated with worse overall prognosis, including NUSAP1, PTTG1, CEP55, TOP2A, CCNB1, CENPF, MELK, AURKA, UBE2C, BUB1B, KIF20A and RRM2.Conclusion: The present study identified 12 target genes associated with the development of HER-2 subtype breast cancer, which may help to provide new biomarkers and therapeutic targets.

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