Transcriptomic profiling revealed key signaling pathways for cold tolerance and acclimation of two carp species

Abstract Background: Closely related species of the carp family (Cyprinidae) have evolved distinctive abilities to survive under cold stress, but molecular mechanisms underlying the generation of cold resistance remain largely unknown. In this study, we compared transcriptomic profiles of two carp species to identify key factors and pathways for cold tolerance and acclimation. Results: Larvae of Songpu mirror carp and Barbless carp that were pretreated at 18°C for 24 hours significantly improved their survival rates under lethal cold temperature at 8°C or 10°C, indicating that two carp species possess the ability of cold acclimation. However, Songpu mirror carp exhibited stronger abilities of cold tolerance and acclimation than Barbless carp. Transcriptomic profiles of Songpu mirror carp and Barbless carp larvae at 28°C and 18°C were compared during cold acclimation through RNA-seq. Differentially expressed genes that are closely associated with the differences in cold acclimation between two carp species were identified through bioinformatics and Venn's diagram analysis. GO enrichment analysis of these genes indicated that cellular component assembly involved in morphogenesis, secondary alcohol metabolism and drug transport were the most up-regulated biological processes during cold acclimation of Songpu mirror carp. Conversely, positive regulation of macroautophagy, intracellular protein transport, and organonitrogen compound catabolism were the most down-regulated biological processes during cold acclimation of Barbless carp. KEGG enrichment analysis revealed that factors in the FoxO-related signaling pathways are mainly responsible for the development of differences in cold tolerance and acclimation between two carp species since altering the phosphorylation of key proteins in the FoxO-related signaling pathways with inhibitors or an activator significantly decreased the cold tolerance and acclimation of Songpu mirror carp. These data provided key clues for dissection of molecular mechanisms underlying the development of cold tolerance and acclimation in carps. Conclusions: These findings indicate that larvae of two carp species possess different abilities of cold tolerance and can build cold acclimation under mild low temperature. Multiple biological processes and FoxO-related signaling pathways are closely associated with the development of differences in cold tolerance and acclimation between two carp species.

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Transcriptomic profiling revealed key signaling pathways for cold tolerance and acclimation of two carp species

10.21203/rs.2.16649/v3 ◽

2020 ◽

Author(s):

Guodong Ge ◽

Yong Long ◽

Lianyu Shi ◽

Jing Ren ◽

Junjun Yan ◽

...

Keyword(s):

Signaling Pathways ◽

Cold Acclimation ◽

Cold Tolerance ◽

Drug Transport ◽

Molecular Mechanisms ◽

Protein Transport ◽

Secondary Alcohol ◽

Enrichment Analysis ◽

Biological Processes ◽

Mirror Carp

Abstract Background Closely related species of the carp family ( Cyprinidae ) have evolved distinctive abilities to survive under cold stress, but molecular mechanisms underlying the generation of cold resistance remain largely unknow. In this study, we compared transcriptomic profiles of two carp species to identify key factors and pathways for cold tolerance and acclimation. Results Larvae of Songpu mirror carp and Barbless carp that were pretreated at 18°C for 24 hours significantly improved their survival rates under lethal cold temperature at 8°C or 10°C, indicating that two carp species possess the ability of cold acclimation. However, Songpu mirror carp exhibited stronger abilities of cold tolerance and acclimation than Barbless carp. Transcriptomic profiles of Songpu mirror carp and Barbless carp larvae at 28°C and 18°C were compared during cold acclimation through RNA-seq. Differentially expressed genes that are closely associated with the differences in cold acclimation between two carp species were identified through bioinformatics and Venn's diagram analysis. GO enrichment analysis of these genes indicated that cellular component assembly involved in morphogenesis, secondary alcohol metabolism and drug transport were the most up-regulated biological processes during cold acclimation of Songpu mirror carp. Conversely, positive regulation of macroautophagy, intracellular protein transport, and organonitrogen compound catabolism were the most down-regulated biological processes during cold acclimation of Barbless carp. KEGG enrichment analysis revealed that factors in the FoxO-related signaling pathways are mainly responsible for the development of differences in cold tolerance and acclimation between two carp species since altering the phosphorylation of key proteins in the FoxO-related signaling pathways with inhibitors or an activator significantly decreased the cold tolerance and acclimation of Songpu mirror carp. These data provided key clues for dissection of molecular mechanisms underlying the development of cold tolerance and acclimation in carps. Conclusions These findings indicate that larvae of two carp species possess different abilities of cold tolerance and can build cold acclimation under mild low temperature. Multiple biological processes and FoxO-related signaling pathways are closely associated with the development of differences in cold tolerance and acclimation between two carp species.

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Transcriptomic profiling revealed key signaling pathways for cold tolerance and acclimation of two carp species

10.21203/rs.2.16649/v1 ◽

2019 ◽

Author(s):

Guodong Ge ◽

Yong Long ◽

Lianyu Shi ◽

Jing Ren ◽

Junjun Yan ◽

...

Keyword(s):

Signaling Pathways ◽

Cold Acclimation ◽

Cold Tolerance ◽

Drug Transport ◽

Molecular Mechanisms ◽

Secondary Alcohol ◽

Enrichment Analysis ◽

Biological Processes ◽

Rna Seq ◽

Mirror Carp

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Network pharmacology and molecular docking study on the active ingredients of qidengmingmu capsule for the treatment of diabetic retinopathy

Scientific Reports ◽

10.1038/s41598-021-86914-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mingxu Zhang ◽

Jiawei Yang ◽

Xiulan Zhao ◽

Ying Zhao ◽

Siquan Zhu

Keyword(s):

Diabetic Retinopathy ◽

Molecular Docking ◽

Molecular Mechanisms ◽

Hypoxia Inducible Factor ◽

Enrichment Analysis ◽

Docking Study ◽

Network Pharmacology ◽

Biological Processes ◽

Active Ingredients ◽

Molecular Docking Study

AbstractDiabetic retinopathy (DR) is a leading cause of irreversible blindness globally. Qidengmingmu Capsule (QC) is a Chinese patent medicine used to treat DR, but the molecular mechanism of the treatment remains unknown. In this study, we identified and validated potential molecular mechanisms involved in the treatment of DR with QC via network pharmacology and molecular docking methods. The results of Ingredient-DR Target Network showed that 134 common targets and 20 active ingredients of QC were involved. According to the results of enrichment analysis, 2307 biological processes and 40 pathways were related to the treatment effects. Most of these processes and pathways were important for cell survival and were associated with many key factors in DR, such as vascular endothelial growth factor-A (VEGFA), hypoxia-inducible factor-1A (HIF-1Α), and tumor necrosis factor-α (TNFα). Based on the results of the PPI network and KEGG enrichment analyses, we selected AKT1, HIF-1α, VEGFA, TNFα and their corresponding active ingredients for molecular docking. According to the molecular docking results, several key targets of DR (including AKT1, HIF-1α, VEGFA, and TNFα) can form stable bonds with the corresponding active ingredients of QC. In conclusion, through network pharmacology methods, we found that potential biological mechanisms involved in the alleviation of DR by QC are related to multiple biological processes and signaling pathways. The molecular docking results also provide us with sound directions for further experiments.

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Integrated lncRNA and mRNA Transcriptome Analyses in the Ovary of Cynoglossus semilaevis Reveal Genes and Pathways Potentially Involved in Reproduction

Frontiers in Genetics ◽

10.3389/fgene.2021.671729 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yani Dong ◽

Likang Lyu ◽

Daiqiang Zhang ◽

Jing Li ◽

Haishen Wen ◽

...

Keyword(s):

Signaling Pathways ◽

Target Genes ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Cynoglossus Semilaevis ◽

Gene Set Enrichment Analysis ◽

Functional Enrichment ◽

Biological Processes ◽

Tongue Sole ◽

Oocyte Meiosis

Long non-coding RNAs (lncRNAs) have been reported to be involved in multiple biological processes. However, the roles of lncRNAs in the reproduction of half-smooth tongue sole (Cynoglossus semilaevis) are unclear, especially in the molecular regulatory mechanism driving ovarian development and ovulation. Thus, to explore the mRNA and lncRNA mechanisms regulating reproduction, we collected tongue sole ovaries in three stages for RNA sequencing. In stage IV vs. V, we identified 312 differentially expressed (DE) mRNAs and 58 DE lncRNAs. In stage V vs. VI, we identified 1,059 DE mRNAs and 187 DE lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DE mRNAs were enriched in ECM-receptor interaction, oocyte meiosis and steroid hormone biosynthesis pathways. Furthermore, we carried out gene set enrichment analysis (GSEA) to identify potential reproduction related-pathways additionally, such as fatty metabolism and retinol metabolism. Based on enrichment analysis, DE mRNAs with a potential role in reproduction were selected and classified into six categories, including signal transduction, cell growth and death, immune response, metabolism, transport and catabolism, and cell junction. The interactions of DE lncRNAs and mRNAs were predicted according to antisense, cis-, and trans-regulatory mechanisms. We constructed a competing endogenous RNA (ceRNA) network. Several lncRNAs were predicted to regulate genes related to reproduction including cyp17a1, cyp19a1, mmp14, pgr, and hsd17b1. The functional enrichment analysis of these target genes of lncRNAs revealed that they were involved in several signaling pathways, such as the TGF-beta, Wnt signaling, and MAPK signaling pathways and reproduction related-pathways such as the progesterone-mediated oocyte maturation, oocyte meiosis, and GnRH signaling pathway. RT-qPCR analysis showed that two lncRNAs (XR_522278.2 and XR_522171.2) were mainly expressed in the ovary. Dual-fluorescence in situ hybridization experiments showed that both XR_522278.2 and XR_522171.2 colocalized with their target genes cyp17a1 and cyp19a1, respectively, in the follicular cell layer. The results further demonstrated that lncRNAs might be involved in the biological processes by modulating gene expression. Taken together, this study provides lncRNA profiles in the ovary of tongue sole and further insight into the role of lncRNA involvement in regulating reproduction in tongue sole.

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Analysis of the Molecular Mechanisms of the Effects of Prunella vulgaris against Subacute Thyroiditis Based on Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9810709 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Xin Shen ◽

Rui Yang ◽

Jianpeng An ◽

Xia Zhong

Keyword(s):

Signaling Pathways ◽

Molecular Mechanisms ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Subacute Thyroiditis ◽

Network Pharmacology ◽

Pharmacokinetic Parameters ◽

Pathway Enrichment Analysis ◽

Prunella Vulgaris ◽

Protein Protein Interaction

Prunella vulgaris (PV) has a long history of application in traditional Chinese and Western medicine as a remedy for the treatment of subacute thyroiditis (SAT). This study applied network pharmacology to elucidate the mechanism of the effects of PV against SAT. Components of the potential therapeutic targets of PV and SAT-related targets were retrieved from databases. To construct a protein-protein interaction (PPI) network, the intersection of SAT-related targets and PV-related targets was input into the STRING platform. Gene ontology (GO) analysis and KEGG pathway enrichment analysis were carried out using the DAVID database. Networks were constructed by Cytoscape for visualization. The results showed that a total of 11 compounds were identified according to the pharmacokinetic parameters of ADME. A total of 126 PV-related targets and 2207 SAT-related targets were collected, and 83 overlapping targets were subsequently obtained. The results of the KEGG pathway and compound-target-pathway (C-T-P) network analysis suggested that the anti-SAT effect of PV mainly occurs through quercetin, luteolin, kaempferol, and beta-sitosterol and is most closely associated with their regulation of inflammation and apoptosis by targeting the PIK3CG, MAPK1, MAPK14, TNF, and PTGS2 proteins and the PI3K-Akt and TNF signaling pathways. The study demonstrated that quercetin, luteolin, kaempferol, and beta-sitosterol in PV may play a major role in the treatment of SAT, which was associated with the regulation of inflammation and apoptosis, by targeting the PI3K-Akt and TNF signaling pathways.

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Dietary Enteromorpha Polysaccharides Supplementation Improves Breast Muscle Yield and Is Associated With Modification of mRNA Transcriptome in Broiler Chickens

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.663988 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yue Zhao ◽

Balamuralikrishnan Balasubramanian ◽

Yan Guo ◽

Sheng-Jian Qiu ◽

Rajesh Jha ◽

...

Keyword(s):

Signaling Pathways ◽

Broiler Chickens ◽

Molecular Mechanisms ◽

Carcass Traits ◽

Enrichment Analysis ◽

Dietary Supplementation ◽

Breast Muscle ◽

Rna Seq ◽

Feeding Trial ◽

Mrna Transcriptome

The present study evaluated the effects of dietary supplementation of Enteromorpha polysaccharides (EP) on carcass traits of broilers and potential molecular mechanisms associated with it. This study used RNA-Sequencing (RNA-Seq) to detect modification in mRNA transcriptome and the cognate biological pathways affecting the carcass traits. A total of 396 one-day-old male broilers (Arbor Acres) were randomly assigned to one of six dietary treatments containing EP at 0 (CON), 1000 (EP_1000), 2500 (EP_2500), 4000 (EP_4000), 5500 (EP_5500), and 7000 (EP_7000) mg/kg levels for a 35-d feeding trial with 6 replicates/treatment. At the end of the feeding trial, six birds (one bird from each replicate cage) were randomly selected from each treatment and slaughtered for carcass traits analysis. The results showed that the dietary supplementation of EP_7000 improved the breast muscle yield (p < 0.05). Subsequently, six breast muscle samples from CON and EP_7000 groups (three samples from each group) were randomly selected for RNA-Seq analysis. Based on the RNA-Seq results, a total of 154 differentially expressed genes (DEGs) were identified (p < 0.05). Among the DEGs, 112 genes were significantly upregulated, whereas 42 genes were significantly down-regulated by EP_7000 supplementation. Gene Ontology enrichment analysis showed that the DEGs were mainly enriched in immune-related signaling pathways, macromolecule biosynthetic, DNA-templated, RNA biosynthetic, and metabolic process (p < 0.05). Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the DEGs were enriched in signaling pathways related to viral infectious diseases and cell adhesion molecules (p < 0.05). In conclusion, dietary inclusion of EP_7000 improves the breast muscle yield, which may be involved in improving the immunity and the cell differentiation of broilers, thus promoting the muscle growth of broilers. These findings could help understand the molecular mechanisms that enhance breast muscle yield by dietary supplementation of EP in broilers.

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Identification and verification of the molecular mechanisms and prognostic values of the cadherin gene family in gastric cancer

Scientific Reports ◽

10.1038/s41598-021-03086-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shanshan Luo ◽

Rujing Lin ◽

Xiwen Liao ◽

Daimou Li ◽

Yuzhou Qin

Keyword(s):

Gastric Cancer ◽

Signaling Pathways ◽

Risk Score ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Study Data ◽

The Cancer Genome Atlas ◽

Risk Scores ◽

Phosphoinositide 3 Kinase ◽

Functional Mechanisms

AbstractWhile cadherin (CDH) genes are aberrantly expressed in cancers, the functions of CDH genes in gastric cancer (GC) remain poorly understood. The clinical significance and molecular mechanisms of CDH genes in GC were assessed in this study. Data from a total of 1226 GC patients included in The Cancer Genome Atlas (TCGA) and Kaplan–Meier plotter database were used to independently explore the value of CDH genes in clinical application. The TCGA RNA sequencing dataset was used to explore the molecular mechanisms of CDH genes in GC. Using enrichment analysis tools, CDH genes were found to be related to cell adhesion and calcium ion binding in function. In TCGA cohort, 12 genes were found to be differentially expressed between GC para-carcinoma and tumor tissue. By analyzing GC patients in two independent cohorts, we identified and verified that CDH2, CDH6, CDH7 and CDH10 were significantly associated with a poor GC prognosis. In addition, CDH2 and CDH6 were used to construct a GC risk score signature that can significantly improve the accuracy of predicting the 5-year survival of GC patients. The GSEA approach was used to explore the functional mechanisms of the four prognostic CDH genes and their associated risk scores. It was found that these genes may be involved in multiple classic cancer-related signaling pathways, such as the Wnt and phosphoinositide 3-kinase signaling pathways in GC. In the subsequent CMap analysis, three small molecule compounds (anisomycin, nystatin and bumetanide) that may be the target molecules that determine the risk score in GC, were initially screened. In conclusion, our current study suggests that four CDH genes can be used as potential biomarkers for GC prognosis. In addition, a prognostic signature based on the CDH2 and CDH6 genes was constructed, and their potential functional mechanisms and drug interactions explored.

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Identification of the Crucial Gene in Overflow Arteriovenous Fistula by Bioinformatics Analysis

Frontiers in Physiology ◽

10.3389/fphys.2021.621830 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhengde Zhao ◽

Qining Fu ◽

Liangzhu Hu ◽

Yangdong Liu

Keyword(s):

Signaling Pathways ◽

Signaling Pathway ◽

Intimal Hyperplasia ◽

Enrichment Analysis ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Biological Processes ◽

Hub Genes ◽

Av Fistula ◽

Core Genes

Objective: The aim was to study the preliminary screening of the crucial genes in intimal hyperplasia in the venous segment of arteriovenous (AV) fistula and the underlying potential molecular mechanisms of intimal hyperplasia with bioinformatics analysis.Methods: The gene expression profile data (GSE39488) was analyzed to identify differentially expressed genes (DEGs). We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs. Gene set enrichment analysis (GSEA) was used to understand the potential activated signaling pathway. The protein–protein interaction (PPI) network was constructed with the STRING database and Cytoscape software. The Venn diagram between 10 hub genes and gene sets of 4 crucial signaling pathways was used to obtain core genes and relevant potential pathways. Furthermore, GSEAs were performed to understand their biological functions.Results: A total of 185 DEGs were screened in this study. The main biological function of the 111 upregulated genes in AV fistula primarily concentrated on cell proliferation and vascular remodeling, and the 74 downregulated genes in AV fistula were enriched in the biological function mainly relevant to inflammation. GSEA found four signaling pathways crucial for intimal hyperplasia, namely, MAPK, NOD-like, Cell Cycle, and TGF-beta signaling pathway. A total of 10 hub genes were identified, namely, EGR1, EGR2, EGR3, NR4A1, NR4A2, DUSP1, CXCR4, ATF3, CCL4, and CYR61. Particularly, DUSP1 and NR4A1 were identified as core genes that potentially participate in the MAPK signaling pathway. In AV fistula, the biological processes and pathways were primarily involved with MAPK signaling pathway and MAPK-mediated pathway with the high expression of DUSP1 and were highly relevant to cell proliferation and inflammation with the low expression of DUSP1. Besides, the biological processes and pathways in AV fistula with the high expression of NR4A1 similarly included the MAPK signaling pathway and the pathway mediated by MAPK signaling, and it was mainly involved with inflammation in AV fistula with the low expression of NR4A1.Conclusion: We screened four potential signaling pathways relevant to intimal hyperplasia and identified 10 hub genes, including two core genes (i.e., DUSP1 and NR4A1). Two core genes potentially participate in the MAPK signaling pathway and might serve as the therapeutic targets of intimal hyperplasia to prevent stenosis after AV fistula creation.

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Identification of Critical Functional Modules and Signaling Pathways in Osteoporosis

Current Bioinformatics ◽

10.2174/1574893615999200706002411 ◽

2020 ◽

Vol 15 ◽

Author(s):

Xiaowei Jiang ◽

Pu Ying ◽

Yingchao Shen ◽

Yiming Miu ◽

Wenbin Kong ◽

...

Keyword(s):

Signaling Pathways ◽

Differential Expression ◽

Expression Analysis ◽

Network Topology ◽

Molecular Mechanisms ◽

Differential Expression Analysis ◽

Osteoclast Differentiation ◽

Enrichment Analysis ◽

Osteoclast Formation ◽

Functional Modules

Background: Osteoporosis is the most common bone metabolic disease. Abnormal osteoclast formation and resorption play a fundamental role in osteoporosis pathogenesis. Recent researches have greatly broadened our understanding of molecular mechanisms of osteoporosis. However, the molecular mechanisms leading to osteoporosis are still not entirely clear. Objective: The purpose of this work is to study the critical regulatory genes, functional modules, and signaling pathways. Methods: Differential expression analysis, network topology-based analysis, and overrepresentation enrichment analysis (ORA) were used to identify differentially expressed genes (DEGs), gene subnetworks, and signaling pathways related to osteoporosis, respectively. Results: Differential expression analysis identified DEGs, such as POGLUT1, DAPK3 and NFKBIA, associated with osteoclastogenesis, which highlighted Notch, apoptosis and NF-kB signaling pathways. Network topology-based analysis identified the upregulated subnetwork characterized by EXOSC8 and DIS3L from the RNA exosome complex, and the downregulated subnetwork composed of histone deacetylases and the cofactors, MORF4L1 and JDP2. Furthermore, the overrepresentation enrichment analysis highlighted that corticotrophin-releasing hormone signaling pathway may affect osteoclastogenesis through its component NR4A1, and suppressing osteoclast differentiation and osteoclast bone resorption with urocortin (UCN). Conclusion: Our systematic analysis not only discovered novel molecular mechanisms, but also proposed potential drug targets for osteoporosis.

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Identification and Verification of the Molecular Mechanisms and Prognostic Values of the Cadherin Gene Family in Gastric Cancer

10.21203/rs.3.rs-78765/v1 ◽

2020 ◽

Author(s):

Shanshan Luo ◽

Xiwen Liao ◽

Xianwei Mo ◽

Daimou Li ◽

Yuzhou Qin

Keyword(s):

Gastric Cancer ◽

Signaling Pathways ◽

Risk Score ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Risk Scores ◽

Kaplan Meier ◽

Phosphoinositide 3 Kinase ◽

Functional Mechanisms

Abstract Background: While cadherin (CDH) genes are aberrantly expressed in cancers, the functions of CDH genes in gastric cancer (GC) remain poorly understood. The clinical significance and molecular mechanisms of CDH genes in GC were assessed in this study.Methods: Data from a total of 1226 GC patients included in The Cancer Genome Atlas (TCGA) and Kaplan-Meier plotter database were used to independently explore the value of CDH genes in clinical application. The TCGA RNA sequencing dataset was used to explore the molecular mechanisms of CDH genes in GC.Results: Using enrichment analysis tools, CDH genes were found to be related to cell adhesion and calcium ion binding in function. In TCGA cohort, 12 genes were found to be differentially expressed between GC para-carcinoma and tumor tissue. By analyzing GC patients in two independent cohorts, we identified and verified that CDH2, CDH6, CDH7 and CDH10 were significantly associated with a poor GC prognosis. In addition, CDH2 and CDH6 were used to construct a GC risk score signature that can significantly improve the accuracy of predicting the 5-year survival of GC patients. The GSEA approach was used to explore the functional mechanisms of the four prognostic CDH genes and their associated risk scores. It was found that these genes may be involved in multiple classic cancer-related signaling pathways, such as the Wnt and phosphoinositide 3-kinase signaling pathways in GC. In the subsequent CMap analysis, three small molecule compounds (anisomycin, nystatin and bumetanide) that may be the target molecules that determine the risk score in GC, were initially screened. Conclusions: Our current study suggests that four CDH genes can be used as potential biomarkers for GC prognosis. In addition, a prognostic signature based on the CDH2 and CDH6 genes was constructed, and their potential functional mechanisms and drug interactions explored.

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