System Pharmacological Mechanism and Compatibility Laws of Jianghuang from Traditional Chinese Medicine In Blood-Regulating Formulae

2020 ◽  
Author(s):  
Zhiqiang Liu ◽  
Bolong Wang
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Kegg Pathway ◽  
Inflammatory Diseases ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Pharmacological Effects ◽  
Ppi Network ◽  
Pathway Enrichment ◽  
Pharmacological Mechanism

Abstract Background: Jianghuang (JH) is a popular ingredient in blood-regulating traditional Chinese Medicine (TCM) that could be effective for the treatment of various diseases. We demonstrate the compatibility laws and system pharmacological mechanisms of the key formula containing JH by leveraging data mining of bioinformatics databases.Material/Methods: The compatibility laws of blood-regulating formulae containing JH from the Chinese Traditional Medicine Formula Dictionary were analyzed using a generalized rule induction (GRI) algorithm implemented. The putative target gene and miRNA were retrieved via a combination of the Arrowsmith knowledge discovery tool and FunRich 3.1.3. System pharmacological mechanisms are traced by their protein-protein interaction (PPI) network, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted using Uniprot, the Human Protein Atlas (HPA), STRING 11.0, and KOBAS 3.0.Results: We found that the JH-CX-DG formula (Ligusticum chuanxiong-Angelica sinensis) could represent a key formula containing JH in blood-regulating TCM formulae. The JH-CX-DG formula was observed to directly target AKT, TLR4, caspase-3, PI3K, mTOR, p38 MAPK, VEGF, iNOS, Nrf2, BDNF, NF-κB, Bcl-2, and Bax 13 targets and regulate targets through 13 miRNA. The PPI network and KEGG pathway enrichment analysis showed that the JH-CX-DG formula possess potential pharmacological effects including anti-inflammatory, improving microcirculation, and anti-tumor through the regulation of multiple pathways including PI3K/Akt, MAPK, Toll-like receptor, T cell receptor, EGFR, VEGFR, Apoptosis, HIF-1 (p < 0.05).Conclusion: The JH-CX-DG formula can exert beneficial pharmacological effects through multi-target and multi-pathway interactions. It can be effectively administered for the treatment of inflammatory diseases, microcirculation disorders, cardiovascular disease, and cancer. We found a new effective drug formula through analyzing the compatibility law and systemic pharmacological mechanism of JH. Our study provides a theoretical basis and directions for subsequent research on the JH-CX-DG formula.

scholarly journals Utilizing network pharmacology to explore the underlying mechanism of Radix Salviae in diabetic retinopathy

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Chun-Li Piao ◽  
Jin-Li Luo ◽  
De Jin ◽  
Cheng Tang ◽  
Li Wang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Chinese Medicine ◽  
Growth Factor ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment ◽  
Underlying Mechanisms

Abstract Introduction Radix Salviae (Dan-shen in pinyin), a classic Chinese herb, has been extensively used to treat diabetic retinopathy in clinical practice in China for many years. However, the pharmacological mechanisms of Radix Salviae remain vague. The aim of this study was to decrypt the underlying mechanisms of Radix Salviae in the treatment of diabetic retinopathy using a systems pharmacology approach. Methods A network pharmacology-based strategy was proposed to elucidate the underlying multi-component, multi-target, and multi-pathway mode of action of Radix Salviae against diabetic retinopathy. First, we collected putative targets of Radix Salviae based on the Traditional Chinese Medicine System Pharmacology database and a network of the interactions among the putative targets of Radix Salviae and known therapeutic targets of diabetic retinopathy was built. Then, two topological parameters, “degree” and “closeness certainty” were calculated to identify the major targets in the network. Furthermore, the major hubs were imported to the Database for Annotation, Visualization and Integrated Discovery to perform a pathway enrichment analysis. Results A total of 130 nodes, including 18 putative targets of Radix Salviae, were observed to be major hubs in terms of topological importance. The results of pathway enrichment analysis indicated that putative targets of Radix Salviae mostly participated in various pathways associated with angiogenesis, protein metabolism, inflammatory response, apoptosis, and cell proliferation. The putative targets of Radix Salviae (vascular endothelial growth factor, matrix metalloproteinases, plasminogen, insulin-like growth factor-1, and cyclooxygenase-2) were recognized as active factors involved in the main biological functions of treatment, which implied that these were involved in the underlying mechanisms of Radix Salviae on diabetic retinopathy. Conclusions Radix Salviae could alleviate diabetic retinopathy via the molecular mechanisms predicted by network pharmacology. This research demonstrates that the network pharmacology approach can be an effective tool to reveal the mechanisms of traditional Chinese medicine from a holistic perspective.

scholarly journals Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Guoxiu Zu ◽  
Keyun Sun ◽  
Ling Li ◽  
Xiuli Zu ◽  
Tao Han ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Pathway Enrichment

AbstractQuercetin has demonstrated antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic activities, suggesting therapeutic potential against type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). In this study, potential molecular targets of quercetin were first identified using the Swiss Target Prediction platform and pathogenic targets of T2DM and AD were identified using online Mendelian inheritance in man (OMIM), DisGeNET, TTD, DrugBank, and GeneCards databases. The 95 targets shared among quercetin, T2DM, and AD were used to establish a protein–protein interaction (PPI) network, top 25 core genes, and protein functional modules using MCODE. Metascape was then used for gene ontology and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. A protein functional module with best score was obtained from the PPI network using CytoHubba, and 6 high-probability quercetin targets (AKT1, JUN, MAPK, TNF, VEGFA, and EGFR) were confirmed by docking simulations. Molecular dynamics simulation was carried out according to the molecular docking results. KEGG pathway enrichment analysis suggested that the major shared mechanisms for T2DM and AD include “AGE-RAGE signaling pathway in diabetic complications,” “pathways in cancer,” and “MAPK signaling pathway” (the key pathway). We speculate that quercetin may have therapeutic applications in T2DM and AD by targeting MAPK signaling, providing a theoretical foundation for future clinical research.

scholarly journals Screening of Osteoarthritis-Related Genes and Function Determination Based on Bioinformatics Tools

2021 ◽  
Author(s):  
Zheng Fu ◽  
Weiqian Jiang ◽  
Wenlong Yan ◽  
Fei Xie ◽  
Yu Chen ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Bioinformatics Analysis ◽  
Kegg Pathway ◽  
Experimental Studies ◽  
Therapeutic Targets ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Pathway Enrichment ◽  
Early Diagnostic

Abstract Background:Osteoarthritis(OA), commonly seen in the middle-aged and elderly population, imposes a heavy burden on patients from the clinical, humanistic and economic aspects. Our work aims at the discovery of early diagnostic and therapeutic targets for OA and new candidate biomarkers for experimental studies on OA via bioinformatics analysis.Methods:The dataset GSE114007 was downloaded from GEO to identify differentially expressed genes(DEGs) in R using 3 different algorithms. Overlapping DEGs were subject to GO and KEGG pathway enrichment analysis and functional annotation. Following the identification of DEGs, a protein-protein interaction(PPI) network was established and imported into Cytoscape to screen for hubgenes. The expression of each hubgene was verified in two other datasets and create miRNA-mRNA regulatory networks.Results:174 upregulated genes and 117 downregulated genes were identified among the overlapping DEGs. According to the results of GO enrichment analysis,MF enrichment was basically found in ECM degradation and collagen breakdown; enrichment was also present in the development, ossification, and differentiation of cells. The KEGG pathway enrichment analysis suggested significant enrichment in such pathways as PI3K-AKT, P53, TNF, and FoxO. 23 hubgenes were obtained from the PPI network, and 11 genes were identified as DEGs through verification. 8 genes were used for the establishment of miRNA-mRNA regulatory networks.Conclusion:OA-related genes, proteins, pathways and miRNAs that were identified through bioinformatics analysis may provide a reference for the discovery of early diagnostic and therapeutic targets for OA, as well as candidate biomarkers for experimental studies on OA.

scholarly journals A network pharmacology and molecular docking study on treatment mechanism of Bacterial Dysentery of Huanglian-Huangqin-Huangbo herb pair

2021 ◽  
Author(s):  
qiaoxin xu ◽  
Xiaojia Wang ◽  
Ning Zhong ◽  
Yue Wang ◽  
Zhong Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Signaling Pathways ◽  
Kegg Pathway ◽  
Function Analysis ◽  
Intestinal Flora ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Active Compounds ◽  
Pathway Enrichment

Abstract Background: Bacillary dysentery (BD) is one of the most common epidemic infectious diseases. Hundreds of millions of people are infected with BD each year among the world. The patients usually have the following symptoms: abdominal pain, diarrhea, intestinal flora imbalance, etc. Antibiotic are widely used for the treatment in clinical practice. However, due to the overuse of antibiotics, the bacterial resistance is increasingly serious and the medical works are facing with the risk that the antibiotics would lose efficacy. Apart from chemical medicines, traditional Chinese medicines (TCM) are also well accepted for BD treatment, especially in Asian countries. Huanglian-Huangqin-Huangbo herb pair (HHH) is typical and commonly used to treat symptoms such as abdominal pain, diarrhea, and intestinal flora imbalance caused by BD. Also, the HHH has antibacterial, anti-inflammatory, and antidiarrheal effects. In this study, we are committed to ascertain the potential active compounds of HHH and the onset mechanism for the treatment of BD.Methods With the help of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (Traditional Chinese Medicine Systems Pharmacology Database, TCMSP) and PubChem database to search and screen the chemical components and targets of Coptis, Scutellaria, Phellodendron, the gene names were corrected through the Uniprot database, and used the CTD database, TTD database, GeneCards database and DRUGBANK database to obtain BD-related disease targets. The online drawing platform Bioinformatics was used to analyze the "active compound-disease" intersection target, and utilized Cyoscape 3.7.2 software to construct a visualized Chinese medicine-active compound-target network and protein interaction network in order to screen the potential key active compounds and key targets; GO function analysis and KEGG pathway enrichment analysis of the target were carried out through the Metascape database platform, and Cyoscape 3.7.2 software was used to construct a gene-pathway network to screen potential pathways and their mechanism of action. Molecular docking of the key active compounds of the HHH with the key target of BD. Results A total of 331 potential active compounds were screened for the HHH, among which 87 key active compounds such as quercetin, wogonin, baicalein, β-sitosterol, isofumarine, and tetrahydroberberine can be selected. Act on BD through 34 potential intersection targets such as IL-6, AKT1, PTGS2, TNF, CASP3, VEGFA, etc. GO gene function analysis yielded a total of 20 biological process (BP) items, 7 cell composition (CC) items, and molecular function (MF) items (P<0.01), mainly involving lipopolysaccharide reaction, reactive oxygen metabolism process, cell factor receptor binding, inorganic substance response, membrane raft, cytokine receptor binding and other biological processes. KEGG pathway enrichment analysis identified 14 signaling pathways (P<0.01), mainly related to cancer signaling pathways, IL-17 signaling pathways and other key pathways. The results of molecular docking HHH owed that the core active components such as quercetin, β-sitosterol, wogonin, isofumarole, baicalein and other core active compounds have good binding effects with the core targets of TNF, IL-6, PTGS2, and BCL2 (binding energy <-5 KJ/mol). Conclusion The effect of HHH on the potential key targets of TNF, IL-6, PTGS2 and other potential key targets through quercetin, β-sitosterol and other potential active compounds to regulate IL-17 and other signaling pathways, thereby exerting therapeutic effects on bacteria. The effect of dysentery is in line with the remarkable characteristics of multi-component, multi-target, and multi-channel effect of Chinese medicine compound.

scholarly journals Mechanism of Quercetin Therapeutic Targets for Alzheimer Disease and type 2 Diabetes Mellitus

2021 ◽  
Author(s):  
Guoxiu Zu ◽  
Keyun Sun ◽  
Ling Li ◽  
Xiuli Zu ◽  
Tao Han ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Pathway Enrichment

Abstract Quercetin has demonstrated antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic activities, suggesting therapeutic potential against type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). In this study, potential molecular targets of quercetin were first identified using the Swiss Target Prediction platform and pathogenic targets of T2DM and AD were identified using Online Mendelian Inheritance in Man (OMIM), DisGeNET, TTD, DrugBank, and GeneCards databases. The 95 targets shared among quercetin, T2DM, and AD were used to establish a protein–protein interaction (PPI) network, top 25 core genes, and protein functional modules using MCODE. Metascape was then used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A protein functional module with best score was obtained from the PPI network using CytoHubba, and 6 high-probability quercetin targets (AKT1, JUN, MAPK, TNF, VEGFA, and EGFR) were confirmed by docking simulations. KEGG pathway enrichment analysis suggested that the major shared mechanisms for T2DM and AD include “AGE-RAGE signaling pathway in diabetic complications,” “pathways in cancer,” and “MAPK signaling pathway” (the key pathway). We speculate that quercetin may have therapeutic applications in T2DM and AD by targeting MAPK signaling, providing a theoretical foundation for future clinical research.

scholarly journals Mechanism of Peony and Licorice and Aconite Decoction in the Treatment of Osteoarthritis Based on Network Pharmacology and Molecular Docking

2021 ◽  
Author(s):  
Zhiqiang li ◽  
Luo Jun
Keyword(s):  
Molecular Docking ◽  
Chinese Medicine ◽  
Protein Interaction ◽  
Active Component ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Pathway Enrichment

Abstract Objective: To predict the key molecular mechanism of Shaoyao Liquorice Aconite Decoction in the treatment of osteoarthritis by using network pharmacology and molecular docking technology, and to provide a new target for the treatment of osteoarthritis. Methods: by means of traditional Chinese medicine database TCMSP screening peony licorice monkshood soup main active component of radix paeoniae alba, radix glycyrrhizae, and the corresponding targets, lateral root of aconite and retrieve OMIM, GeneCards, TDD, PharmGKB and Drugbank database related target for treatment of osteoarthritis, and then forecast drug targets and disease targets for intersection get peony licorice monkshood soup targets for the treatment of osteoarthritis.Then, STRING database and Cytoscape software were used to construct the "drug active component - action target" network and protein interaction network of Shaoyaogaofuzi Decoction in the treatment of osteoarthritis, and David database was used for GO function enrichment analysis and KEGG pathway enrichment analysis of shaoyaogaofuzi Decoction in the treatment of osteoarthritis.Finally, PyMOL, Chem3D, AutoDock, OpenBabel and other software were used to verify the molecular docking of the key active ingredients and key targets of Shaoyao Liquorice Aconite Decoction. Results: 162 active components were screened out.A total of 954 disease targets were collected, and a total of 72 disease targets were obtained after weight removal.Protein interaction analysis suggested that TNF, AKT1, IL6, IL1B and TP53 were the core targets of protein interaction network.Through GO enrichment analysis, 393 biological processes were obtained, and it was found that biological processes were mainly enriched in cell differentiation, migration, apoptosis, and cell stress response to organisms.A total of 116 Pathways were obtained through KEGG pathway enrichment analysis, mainly involving Pathways in cancer, TNF Signaling Pathway, Tuberculosis, Chagas disease, Hepatitis B, etc. Finally, the molecular docking of key active molecules and key targets was realized for verification.Conclusions: this study of compound Chinese medicine pharmacology, through the network of peony licorice monkshood soup ingredients with osteoarthritis, targets, pathway analysis, you can see that drugs in the treatment of osteoarthritis is not a simple single targeted therapy, but by many components, multi-channel, mutual communications between the multiple targets, on the treatment of osteoarthritis in the future to provide more advice.

scholarly journals Replacements of Rare Herbs and Simplifications of Traditional Chinese Medicine Formulae Based on Attribute Similarities and Pathway Enrichment Analysis

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Zhao Fang ◽  
Meixia Zhang ◽  
Zhenghui Yi ◽  
Chengping Wen ◽  
Min Qian ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Enrichment Analysis ◽  
Rapid Decline ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment ◽  
New Approaches ◽  
Forsythia Suspensa ◽  
New Formula ◽  
Wide Usage

A Traditional Chinese Medicine (TCM) formula is a collection of several herbs. TCM formulae have been used to treat various diseases for several thousand years. However, wide usage of TCM formulae has results in rapid decline of some rare herbs. So it is urgent to find common available replacements for those rare herbs with the similar effects. In addition, a formula can be simplified by reducing herbs with unchanged effects. Based on this consideration, we propose a method, called “formula pair,” to replace the rare herbs and simplify TCM formulae. We show its reasonableness from a perspective of pathway enrichment analysis. Both the replacements of rare herbs and simplifications of formulae provide new approaches for a new formula discovery. We demonstrate our approach by replacing a rare herb “Forsythia suspensa” in the formula “the seventh of Sang Ju Yin plus/minus herbs (SSJY)” with a common herb “Thunberg Fritillary Bulb” and simplifying two formulae, “the fifth of Du Huo Ji Sheng Tang plus/minus herbs (FDHJST)” and “Fang Feng Tang” (FFT) to a new formula “Fang Feng Du Huo Tang” (FFDHT).

scholarly journals Exploring the mechanism of Shengmai Yin for coronary heart disease based on systematic pharmacology and chemoinformatics

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Yan Jiang ◽  
Qi He ◽  
Tianqing Zhang ◽  
Wang Xiang ◽  
Zhiyong Long ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Animal Experiments ◽  
Lipid Peroxide ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Shengmai Injection

Abstract Objective: To explore the mechanism of Shengmai Yin (SMY) for coronary heart disease (CHD) by systemic pharmacology and chemoinformatics. Methods: Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), traditional Chinese medicine integrative database (TCMID) and the traditional Chinese medicine (TCM) Database@Taiwan were used to screen and predict the bioactive components of SMY. Pharmmapper were utilized to predict the potential targets of SMY, the TCMSP was utilized to obtain the known targets of SMY. The Genecards and OMIM database were utilized to collect CHD genes. Cytoscape was then used for network construction and analysis, and DAVID was used for Gene Ontology (GO) and pathway enrichment analysis. After that, animal experiments were then performed to further validate the results of systemic pharmacology and chemoinformatics. Results: Three major networks were constructed: (1) CHD genes’ protein–protein interaction (PPI) network; (2) SMY–CHD PPI network; (3) SMY known target–CHD PPI network. The other networks are minor networks generated by analyzing the three major networks. Experimental results showed that compared with the model group, the Shengmai injection (SMI) can reduce the myocardial injury score and the activities of serum aspartate aminoconvertase (AST), CK and lactate dehydrogenase (LDH) in rats (P&lt;0.05), and reduce serum lipid peroxide (LPO) content and increase serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in myocardial infarction rats (P&lt;0.05). SMI can also decrease the expression of MMP-9 mRNA and increase that of TIMP-1 mRNA (P&lt;0.01). Conclusion: SMY may regulate the signaling pathways (such as PPAR, FoxO, VEGF signaling), biological processes (such as angiogenesis, blood pressure formation, inflammatory response) and targets (such as AKT1, EGFR, MAPK1) so as to play a therapeutic role in CHD.

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

scholarly journals Identification of Key Deregulated RNA-Binding Proteins in Pancreatic Cancer by Meta-Analysis and Prediction of Their Role as Modulators of Oncogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Moumita Mukherjee ◽  
Srikanta Goswami
Keyword(s):  
Pancreatic Cancer ◽  
Cell Migration ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Pathway Enrichment

RNA-binding proteins (RBPs) play a significant role in multiple cellular processes with their deregulations strongly associated with cancer. However, there are not adequate evidences regarding global alteration and functions of RBPs in pancreatic cancer, interrogated in a systematic manner. In this study, we have prepared an exhaustive list of RBPs from multiple sources, downloaded gene expression microarray data from a total of 241 pancreatic tumors and 124 normal pancreatic tissues, performed a meta-analysis, and obtained differentially expressed RBPs (DE-RBPs) using the Limma package of R Bioconductor. The results were validated in microarray datasets and the Cancer Genome Atlas (TCGA) RNA sequencing dataset for pancreatic adenocarcinoma (PAAD). Pathway enrichment analysis was performed using DE-RBPs, and we also constructed the protein–protein interaction (PPI) network to detect key modules and hub-RBPs. Coding and noncoding targets for top altered and hub RBPs were identified, and altered pathways modulated by these targets were also investigated. Our meta-analysis identified 45 upregulated and 15 downregulated RBPs as differentially expressed in pancreatic cancer, and pathway enrichment analysis demonstrated their important contribution in tumor development. As a result of PPI network analysis, 26 hub RBPs were detected and coding and noncoding targets for all these RBPs were categorized. Functional exploration characterized the pathways related to epithelial-to-mesenchymal transition (EMT), cell migration, and metastasis to emerge as major pathways interfered by the targets of these RBPs. Our study identified a unique meta-signature of 26 hub-RBPs to primarily modulate pancreatic tumor cell migration and metastasis in pancreatic cancer. IGF2BP3, ISG20, NIP7, PRDX1, RCC2, RUVBL1, SNRPD1, PAIP2B, and SIDT2 were found to play the most prominent role in the regulation of EMT in the process. The findings not only contribute to understand the biology of RBPs in pancreatic cancer but also to evaluate their candidature as possible therapeutic targets.

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