scholarly journals Identification of Key Pathways and Genes Related to the Development of Hair Follicle Cycle in Cashmere Goats

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 180
Author(s):  
Jianfang Wang ◽  
Jie Sui ◽  
Chao Mao ◽  
Xiaorui Li ◽  
Xingyi Chen ◽  
...  

The development of hair follicle in cashmere goats shows significant periodic change, as with mice and humans. However, for cashmere goat with double-coat, the periodic change may be due to other regulatory molecules and signal pathways. To understand the mechanism of periodic development of hair follicle, we performed a weighted gene coexpression network analysis (WGCNA) to mine key genes and establish an interaction network by utilizing the NCBI public dataset. Ten coexpression modules, including 7689 protein-coding genes, were constructed by WGCNA, six of which are considered to be significantly related to the development of the hair follicle cycle. A functional enrichment analysis for each model showed that they are closely related to ECM- receptor interaction, focal adhesion, PI3K-Akt signaling pathway, estrogen signaling pathway, and so on. Combined with the analysis of differential expressed genes, 12 hub genes from coexpression modules were selected as candidate markers, i.e., COL1A1, C1QTNF6, COL1A2, AQP3, KRTAP3-1, KRTAP11-1, FA2H, NDUFS5, DERL2, MRPL14, ANTKMT and XAB2, which might be applied to improve cashmere production.

2020 ◽  
Author(s):  
SANGEETA KUMARI

Abstract Objective This study’s primary goal is unraveling the mechanism of action of bioactives of Curcuma longa L. at the molecular level using protein-protein interaction network.Results We used target proteins to create protein-protein interaction network (PPIN) and identified significant node and edge attributes of PPIN. We identified the cluster of proteins in the PPIN, which were used to identify enriched pathways. . We identified closeness centrality and jaccard score as most important node and edge attribute of the PPIN respectively. The enriched pathways of various clusters were overlapped suggesting synergistic mechanism of action. The three pathways found to be common among three clusters were Gonadotropin-releasing hormone receptor pathway, Endothelin signaling pathway, and Inflammation mediated by chemokine and cytokine signaling pathway.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243507
Author(s):  
Zhihong Wu ◽  
Erhan Hai ◽  
Zhengyang Di ◽  
Rong Ma ◽  
Fangzheng Shang ◽  
...  

Objective Mature hair follicles represent an important stage of hair follicle development, which determines the stability of hair follicle structure and its ability to enter the hair cycle. Here, we used weighted gene co-expression network analysis (WGCNA) to identify hub genes of mature skin and hair follicles in Inner Mongolian cashmere goats. Methods We used transcriptome sequencing data for the skin of Inner Mongolian cashmere goats from fetal days 45–135 days, and divided the co expressed genes into different modules by WGCNA. Characteristic values were used to screen out modules that were highly expressed in mature skin follicles. Module hub genes were then selected based on the correlation coefficients between the gene and module eigenvalue, gene connectivity, and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The results were confirmed by quantitative polymerase chain reaction (qPCR). Results Ten modules were successfully defined, of which one, with a total of 3166 genes, was selected as a specific module through sample and gene expression pattern analyses. A total of 584 candidate hub genes in the module were screened by the correlation coefficients between the genes and module eigenvalue and gene connectivity. Finally, GO/KEGG functional enrichment analyses detected WNT10A as a key gene in the development and maturation of skin hair follicles in fetal Inner Mongolian cashmere goats. qPCR showed that the expression trends of 13 genes from seven fetal skin samples were consistent with the sequencing results, indicating that the sequencing results were reliable.n


2021 ◽  
Vol 12 ◽  
Author(s):  
Fangzheng Shang ◽  
Yu Wang ◽  
Rong Ma ◽  
Zhengyang Di ◽  
Zhihong Wu ◽  
...  

BackgroundInner Mongolian cashmere goats have hair of excellent quality and high economic value, and the skin hair follicle traits of cashmere goats have a direct and important effect on cashmere yield and quality. Circular RNA has been studied in a variety of tissues and cells.ResultIn this study, high-throughput sequencing was used to obtain the expression profiles of circular RNA (circRNA) in the hair follicles of Inner Mongolian cashmere goats at different embryonic stages (45, 55, 65, and 75 days). A total of 21,784 circRNAs were identified. At the same time, the differentially expressed circRNA in the six comparison groups formed in the four stages were: d75vsd45, 59 upregulated and 33 downregulated DE circRNAs; d75vsd55, 61 upregulated and 102 downregulated DE circRNAs; d75vsd65, 32 upregulated and 33 downregulated DE circRNAs; d65vsd55, 67 upregulated and 169 downregulated DE circRNAs; d65vsd45, 96 upregulated and 63 downregulated DE circRNAs; and d55vsd45, 76 upregulated and 42 downregulated DE circRNAs. Six DE circRNA were randomly selected to verify the reliability of the sequencing results by quantitative RT-PCR. Subsequently, the circRNA corresponding host genes were analyzed by the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The results showed that the biological processes related to hair follicle growth and development enriched by GO mainly included hair follicle morphogenesis and cell development, and the signaling pathways related to hair follicle development included the Notch signaling pathway and NF-κB signaling pathway. We combined the DE circRNA of d75vsd45 with miRNA and mRNA databases (unpublished) to construct the regulatory network of circRNA–miRNA–mRNA, and formed a total of 102 pairs of circRNA–miRNA and 126 pairs of miRNA–mRNA interactions. The binding relationship of circRNA3236–chi-miR-27b-3p and circRNA3236–chi-miR-16b-3p was further verified by dual-luciferase reporter assays, and the results showed that circRNA3236 and chi-miR-27b-3p, and circRNA3236 and chi-miR-16b-3p have a targeted binding relationship.ConclusionTo summarize, we established the expression profiling of circRNA in the fetal skin hair follicles of cashmere goats, and found that the host gene of circRNA may be involved in the development of hair follicles of cashmere goats. The regulatory network of circRNA–miRNA–mRNA was constructed and preliminarily verified using DE circRNAs.


Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 429 ◽  
Author(s):  
Zou ◽  
Zheng ◽  
Deng ◽  
Yang ◽  
Xie ◽  
...  

Circular RNA CDR1as/ciRS-7 functions as an oncogenic regulator in various cancers. However, there has been a lack of systematic and comprehensive analysis to further elucidate its underlying role in cancer. In the current study, we firstly performed a bioinformatics analysis of CDR1as among 868 cancer samples by using RNA-seq datasets of the MiOncoCirc database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), CIBERSORT, Estimating the Proportion of Immune and Cancer cells (EPIC), and the MAlignant Tumors using Expression data (ESTIMATE) algorithm were applied to investigate the underlying functions and pathways. Functional enrichment analysis suggested that CDR1as has roles associated with angiogenesis, extracellular matrix (ECM) organization, integrin binding, and collagen binding. Moreover, pathway analysis indicated that it may regulate the TGF-β signaling pathway and ECM-receptor interaction. Therefore, we used CIBERSORT, EPIC, and the ESTIMATE algorithm to investigate the association between CDR1as expression and the tumor microenvironment. Our data strongly suggest that CDR1as may play a specific role in immune and stromal cell infiltration in tumor tissue, especially those of CD8+ T cells, activated NK cells, M2 macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells. Generally, systematic and comprehensive analyses of CDR1as were conducted to shed light on its underlying pro-cancerous mechanism. CDR1as regulates the TGF-β signaling pathway and ECM-receptor interaction to serve as a mediator in alteration of the tumor microenvironment.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Wenqing Nai ◽  
Diane Threapleton ◽  
Jingbo Lu ◽  
Kewei Zhang ◽  
Hongyuan Wu ◽  
...  

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.


2021 ◽  
Author(s):  
Yuanyuan Tian ◽  
Jiao Zhao ◽  
Ju Huang ◽  
Haiying Zhang ◽  
Fushun Ni ◽  
...  

Abstract Background:Tumor endothelial cells (TECs) play an indispensable role in tumor growth and metastasis. Compared with normal endothelial cells (NECs), TECs exhibit unique phenotypic and functional heterogeneity in terms of metabolism, genetics, and transcriptomics. It is not only the key to coordinate tumor angiogenesis, but also an important factor of immune regulation in the tumor microenvironment. In recent years, the role of TECs in tumor metabolism and invasion has been continuously reported. However, the research on the mechanism behind the complex functions of TECs is still at the basic stage. We use Oxford Nanopore Technology (ONT) three-generation full-length transcriptome sequencing to detect all genetic structural changes in the transcriptome of mouse TECs 2H-11 and mouse NECs SVEC4-10.Results: In Tumor endothelial cells 2H-11,1847genes are up-regulated and 1202 genes are down-regulated. According to the Gene ontology (GO) enrichment analysis of differentially expressed genes (DEGs), we found that different functional trends related to metabolic processes, developmental processes, localization, immune system processes, and locomotion are the main reasons for the differences. DEGs are mainly enriched in signal pathways related to cancer, immunity and metabolism, involving Pathways in cancer,Antigen processing and presentation , Proteoglycans in cancer, Focal adhesion, MAPK signaling pathway ,Protein digestion and absorption,ECM-receptor interaction,PI3K-Akt signaling pathway and Glutathione metabolism. We also obtained the structural variation of transcripts such as alternative splicing, gene fusion, and alternative polyadenylation and accurately quantified the expression of the transcript. Some of our results have been confirmed in other documents. But other data have not been reported yet, which is the focus of our future exploration.Conclusion: We try to use transcriptomics and bioinformatics methods to characterize tumor endothelial cell-related genes and signaling pathways.It could help better understand the molecular mechanisms of tumor endothelial cells involved in tumorigenesis and development. DEGs in key pathways may be potential diagnostic markers or therapeutic targets of TECs. Our data also provide useful genetic resources for improving the genome and transcriptome annotations of TECs and NECs.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Shaxi Ouyang ◽  
Yifang Liu ◽  
Changjuan Xiao ◽  
Qinghua Zeng ◽  
Xun Luo ◽  
...  

Introduction. Dermatomyositis (DM) is a chronic autoimmune disease of predominantly lymphocytic infiltration mainly involving the transverse muscle. Its pathogenesis is remaining unknown. This research is designed to probe the latent pathogenesis of dermatomyositis, identify potential biomarkers, and reveal the pathogenesis of dermatomyositis through information biology analysis of gene chips. Methods. In this study, we utilised the GSE14287 and GSE11971 datasets rooted in the Gene Expression Omnibus (GEO) databank, which included a total of 62 DM samples and 9 normal samples. The datasets were combined, and the differentially expressed gene sets were subjected to weighted gene coexpression network analysis, and the hub gene was screened using a protein interaction network from genes in modules highly correlated with dermatomyositis progression. Results. A total of 3 key genes—myxovirus resistance-2 (MX2), oligoadenylate synthetase 1 (OAS1), and oligoadenylate synthetase 2 (OAS2)—were identified in combination with cell line samples, and the expressions of the 3 genes were verified separately. The results showed that MX2, OAS1, and OAS2 were highly expressed in LPS-treated cell lines compared to normal cell lines. The results of pathway enrichment analysis of the genes indicated that all 3 genes were enriched in the cytosolic DNA signalling and cytokine and cytokine receptor interaction signalling pathways; the results of functional enrichment analysis showed that all 3 were enriched in interferon-α response and interferon-γ response functions. Conclusions. This is important for the study of the pathogenesis and objective treatment of dermatomyositis and provides important reference information for the targeted therapy of dermatomyositis.


2020 ◽  
Author(s):  
Yunfei Song ◽  
Jianbo Yang ◽  
Wenguang Jing ◽  
Qi Wang ◽  
Yue Liu ◽  
...  

Abstract Background: Diabetes is a complex metabolic disease characterized by hyperglycemia, plaguing the whole world. However, the action mode of multi-component and multi-target for traditional Chinese medicine (TCM) could be a promising treatment of diabetes mellitus. According to the previous research, the TCM of polygonum multiflorum (PM) showed noteworthy hypoglycemic effect. Up to now, its hypoglycemic active ingredients and mechanism of action are not yet clear. In this study, network pharmacology was employed to elucidate the potential bioactive compounds and hypoglycemic mechanism of Polygonum multiflorum (PM).Methods: First, the compounds with good pharmacokinetic properties were screened from the self-established library of PM, and the targets of these compounds were predicted and collected through database. Relevant targets of diabetes were summarized by searching database. The intersection targets of compound-targets and disease-targets were obtained soon. Secondly, the interaction net between the compounds and the filtered targets was established. These key targets were enriched and analyzed by PPI analysis, molecular docking verification. Finally, the key genes were used to find the biologic pathway and explain the therapeutic mechanism by GO and KEGG analysis. Results: In this study, 29 hypoglycemic components and 63 hypoglycemic targets of PM were filtrated based on online network database. Then the component-target interaction network was constructed and five key components resveratrol, apigenin, kaempferol, quercetin and luteolin were further obtained. Sequential studies turned out, AKT1, EGFR, ESR1, PTGS2, MMP9, MAPK14, and KDR were the common key targets. Docking studies indicated that the bioactive compounds could stably bind the pockets of target proteins. There were 38 metabolic pathways, including regulation of lipolysis in adipocytes, prolactin signaling pathway, TNF signaling pathway, VEGF signaling pathway, FoxO signaling pathway, estrogen signaling pathway, linoleic acid metabolism, Rap1 signaling pathway, arachidonic acid metabolism, and osteoclast differentiation closely connected with the hypoglycemic mechanism of PM.Conclusion: In summary, the study used systems pharmacology to elucidate the main hypoglycemic components and mechanism of PM. The work provided a scientific basis for the further hypoglycemic effect research of PM and its monomer components, but also provided a reference for the secondary development of PM.


2020 ◽  
Author(s):  
Fangzheng Shang ◽  
Yu Wang ◽  
Rong Ma ◽  
Zhengyang Di ◽  
Zhihong Wu ◽  
...  

Abstract Background:Inner Mongolian cashmere goats have hair of excellent quality and high economic value, and the skin hair follicle traits of cashmere goats have a direct and important effect on cashmere yield and quality.Circular RNA has been studied in a variety of tissues and cells. Result:In this study, high-throughput sequencing was used to obtain the expression profiles of circRNA in the hair follicles of Inner Mongolia cashmere goats at different embryonic stages (45, 55 , 65 and 75 days). A total of 21784 circRNAs were identified. At the same time, the differentially expression circRNA in the six control groups formed in the four stages were: d75vsd45, circRNA up-regulated by 59 and down-regulated by 33; d75vsd55, circRNA up-regulated by 61 and down-regulated by 102; d75vsd65, circRNA up-regulated by 32 and down-regulated by 33; d65vsd55, circRNA up-regulated by 67 and down-regulated by 169; d65vsd45, circRNA up-regulated by 96 and down-regulated by 63; and d55vsd45, circRNA up-regulated by 76 and down-regulated by 42. Six DE circRNA were randomly selected to verify the reliability of the sequencing results by qRT-PCR. Subsequently,the circRNA corresponding host genes were analyzed by GO and the KEGG pathaway. The results showed that the biological processes related to hair follicle growth and development enriched by GO mainly included hair follicle morphogenesis, hair follicle maturation and cell development, and the signal pathways related to hair follicle development included the Notch signaling pathway and NF-kappa B signaling pathway.We combined the DE circRNA of d75vsd45 with miRNA and mRNA databases(unpublished) to construct the co-expression network of circRNA-miRNA-mRNA, and formed a total of 102 pairs of circRNA-miRNA and 126 pairs of miRNA-mRNA interactions. The binding relationship of circRNA3236-chi-miR-27b-3p and circRNA3236-chi-miR-16b-3p was further verified by dual-luciferase reporter assays,and the results showed that circRNA3236 and chi-miR-27b-3p,circRNA3236 and chi-miR-16b-3p have a targeted binding relationship.Conclusion:To summarize, we established the expression profile of circRNA in the fetal skin hair follicles of cashmere goats, and found that the host gene of circRNA may be involved in the development of hair follicles of cashmere goats. The co-expression network of circRNA-miRNA-mRNA that DE circRNA was constructed and preliminary verification was carried out.


2020 ◽  
Author(s):  
Yunfei Song ◽  
Jianbo Yang ◽  
Wenguang Jing ◽  
Qi Wang ◽  
Yue Liu ◽  
...  

Abstract Background: Diabetes is a complex metabolic disease characterized by hyperglycemia, plaguing the whole world. However, the action mode of multi-component and multi-target for traditional Chinese medicine (TCM) could be a promising treatment of diabetes mellitus. According to the previous research, the TCM of polygonum multiflorum (PM) showed noteworthy hypoglycemic effect. Up to now, its hypoglycemic active ingredients and mechanism of action are not yet clear. In this study, network pharmacology was employed to elucidate the potential bioactive compounds and hypoglycemic mechanism of Polygonum multiflorum (PM).Methods: First, the compounds with good pharmacokinetic properties were screened from the self-established library of PM, and the targets of these compounds were predicted and collected through database. Relevant targets of diabetes were summarized by searching database. The intersection targets of compound-targets and disease-targets were obtained soon. Secondly, the interaction net between the compounds and the filtered targets was established. These key targets were enriched and analyzed by PPI analysis, molecular docking verification. Thirdly, the key genes were used to find the biologic pathway and explain the therapeutic mechanism by GO and KEGG analysis. Lastly, the part of potential bioactive compounds were under enzyme activity inhibition tests.Results: In this study, 29 hypoglycemic components and 63 hypoglycemic targets of PM were filtrated based on online network database. Then the component-target interaction network was constructed and five key components resveratrol, apigenin, kaempferol, quercetin and luteolin were further obtained. Sequential studies turned out, AKT1, EGFR, ESR1, PTGS2, MMP9, MAPK14, and KDR were the common key targets. Docking studies indicated that the bioactive compounds could stably bind the pockets of target proteins. There were 38 metabolic pathways, including regulation of lipolysis in adipocytes, prolactin signaling pathway, TNF signaling pathway, VEGF signaling pathway, FoxO signaling pathway, estrogen signaling pathway, linoleic acid metabolism, Rap1 signaling pathway, arachidonic acid metabolism, and osteoclast differentiation closely connected with the hypoglycemic mechanism of PM.Conclusion: In summary, the study used systems pharmacology to elucidate the main hypoglycemic components and mechanism of PM. The work provided a scientific basis for the further hypoglycemic effect research of PM and its monomer components, but also provided a reference for the secondary development of PM.


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