scholarly journals Construction and analysis of mRNA, miRNA, lncRNA, and TF regulatory networks reveal the key genes in prostate cancer

2018 ◽  
Author(s):  
Su-Liang Li ◽  
Yun Ye ◽  
Sheng-Yu Wang
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Scale Effects ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Regulation Of Transcription ◽  
Normal Prostate ◽  
Ppi Networks

AbstractPurpose: Prostate cancer (PCa) causes a common male urinary system malignant tumour, and the molecular mechanisms of PCa remain poorly understood. This study aims to investigate the underlying molecular mechanisms of PCa with bioinformatics.Methods: Original gene expression profiles were obtained from the GSE64318 and GSE46602 datasets in the Gene Expression Omnibus (GEO). We conducted differential screens of the expression of genes (DEGs) between two groups using the R software limma package. The interactions between the differentially expressed miRNAs, mRNAs and lncRNAs were predicted and merged with the target genes. Co-expression of the miRNAs, lncRNAs and mRNAs were selected to construct the mRNA-miRNA and-lncRNA interaction networks. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the DEGs. The protein-protein interaction (PPI) networks were constructed, and the transcription factors were annotated. The expression of hub genes in the TCGA datasets was verified to improve the reliability of our analysis.Results: The results demonstrated that 60 miRNAs, 1578 mRNAs and 61 lncRNAs were differentially expressed in PCa. The mRNA-miRNA-lncRNA networks were composed of 5 miRNA nodes, 13 lncRNA nodes, and 45 mRNA nodes. The DEGs were mainly enriched in the nuclei and cytoplasm and were involved in the regulation of transcription, related to sequence-specific DNA binding, and participated in the regulation of the PI3K-Akt signalling pathway. These pathways are related to cancer and focal adhesion signalling pathways. Furthermore, we found that 5 miRNAs, 6 lncRNAs, 6 mRNAs and 2 TFs play important regulatory roles in the interaction network. The expression levels of EGFR, VEGFA, PIK3R1, DLG4, TGFBR1 and KIT were significantly different between PCa and normal prostate tissue.Conclusion: Based on the current study, large-scale effects of interrelated mRNAs, miRNAs, lncRNAs, and TFs were revealed and a model for predicting the mechanism of PCa was provided. This study provides new insight for the exploration of the molecular mechanisms of PCa and valuable clues for further research.

scholarly journals Insight into Molecular Profile Changes after Skeletal Muscle Contusion Using Microarray and Bioinformatics Analyses

2020 ◽  
Author(s):  
Na Li ◽  
Ru-feng Bai ◽  
Chun Li ◽  
Li-hong Dang ◽  
Qiu-xiang Du ◽  
...  
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Healing Process ◽  
Differentially Expressed ◽  
Molecular Profile ◽  
Wound Age ◽  
Functional Modules

Abstract Background: Muscle trauma frequently occurs in daily life. However, the molecular mechanisms of muscle healing, which partly depend on the extent of the damage, are not well understood. This study aimed to investigate gene expression profiles following mild and severe muscle contusion, and to provide more information about the molecular mechanisms underlying the repair process.Methods: A total of 33 rats were divided randomly into control (n = 3), mild contusion (n = 15), and severe contusion (n = 15) groups; the contusion groups were further divided into five subgroups (1, 3, 24, 48, and 168 h post-injury; n = 3 per subgroup). Then full genome microarray of RNA isolated from muscle tissue was performed to access the gene expression changes during healing process.Results: A total of 2,844 and 2,298 differentially expressed genes were identified in the mild and severe contusion groups, respectively. The analysis of the overlapping differentially expressed genes showed that there are common mechanisms of transcriptomic repair of mild and severe contusion within 48 h post-contusion. This was supported by the results of principal component analysis, hierarchical clustering, and weighted gene co‐expression network analysis of the 1,620 coexpressed genes in mildly and severely contused muscle. From these analyses, we discovered that the gene profiles in functional modules and temporal clusters were similar between the mild and severe contusion groups; moreover, the genes showed time-dependent patterns of expression, which allowed us to identify useful markers of wound age. We then performed an analysis of the functions of genes (including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway annotation, and protein–protein interaction network analysis) in the functional modules and temporal clusters, and the hub genes in each module–cluster pair were identified. Interestingly, we found that genes downregulated within 24−48 h of the healing process were largely associated with metabolic processes, especially oxidative phosphorylation of reduced nicotinamide adenine dinucleotide phosphate, which has been rarely reported. Conclusions: These results improve our understanding of the molecular mechanisms underlying muscle repair, and provide a basis for further studies of wound age estimation.

A Comprehensive Data Analysis of Differentially Regulated Genes in Melanoma

2020 ◽  
Author(s):  
Yanjie Han ◽  
Xinxin Li ◽  
Jiliang Yan ◽  
Chunyan Ma ◽  
Xin Wang ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Growth Factor Receptor ◽  
Principal Component ◽  
Distant Metastases ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Ppi Networks

Abstract Background: Melanoma is the most deadly tumor in skin tumors and is prone to distant metastases. The incidence of melanoma has increased rapidly in the past few decades, and current trends indicate that this growth is continuing. This study was aimed to explore the molecular mechanisms of melanoma pathogenesis and discover underlying pathways and genes associated with melanoma.Methods: We used high-throughput expression data to study differential expression profiles of related genes in melanoma. The differentially expressed genes (DEGs) of melanoma in GSE15605, GSE46517, GSE7553 and the Cancer Genome Atlas (TCGA) datasets were analyzed. Differentially expressed genes (DEGs) were identified by paired t-test. Then the DEGs were performed cluster and principal component analyses and protein–protein interaction (PPI) network construction. After that, we analyzed the differential genes through bioinformatics and got hub genes. Finally, the expression of hub genes was confirmed in the TCGA databases and collected patient tissue samples.Results: Total 144 up-regulated DEGs and 16 down-regulated DEGs were identified. A total of 17 gene ontology analysis (GO) terms and 11 pathways were closely related to melanoma. Pathway of pathways in cancer was enriched in 8 DEGs, such as junction plakoglobin (JUP) and epidermal growth factor receptor (EGFR). In the PPI networks, 9 hub genes were obtained, such as loricrin (LOR), filaggrin (FLG), keratin 5 (KRT5), corneodesmosin (CDSN), desmoglein 1 (DSG1), desmoglein 3 (DSG3), keratin 1 (KRT1), involucrin (IVL) and EGFR. The pathway of pathways in cancer and its enriched DEGs may play important roles in the process of melanoma. The hub genes of DEGs may become promising melanoma candidate genes. Five key genes FLG, DSG1, DSG3, IVL and EGFR were identified in the TCGA database and melanoma tissues.Conclusions: The results suggested that FLG, DSG1, DSG3, IVL and EGFR might play important roles and potentially be valuable in the prognosis and treatment of melanoma.

Role of homeobox pathway in prostate carcinogenesis.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 126-126
Author(s):  
James Lin Chen ◽  
Kristen Otto ◽  
Donald Vander Griend
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Seminal Vesicle ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Protein Network ◽  
Gene Profiling ◽  
Normal Prostate ◽  
Survival Difference

126 Background: Identifying aberrant activity of developmental pathways in prostate cancer provides therapeutic opportunities. To this end, despite a shared embryonic origin and similarities to prostate cancer in histology and androgen dependence, seminal vesicle cancer is exceptionally rare. Genomic pathway analyses of their critical developmental differences may reveal uncharacterized oncogenic pathways. Previous attempts to do so have used whole tissue preparations. We hypothesized that careful gene profiling of pure primary epithelial cultures from normal prostate and seminal vesicles would reduce confounding noise during analysis and provide more robust pathway prioritization. Methods: Paired normal prostate and seminal vesicle epithelium cultures were created from three de-identified patients. Derived gene expression profiles were grouped into cancer biomodules using a protein-protein network algorithm to analyze their relationship to known oncogenes. Each resultant biomodule was assayed for its prognostic ability in independent Kaplan-Meier analyses of prostate cancer patients for time to recurrence and overall survival. Protein products from prioritized biomodule genes were then evaluated in vitro. Results: Gene expression profiling and protein network prioritization resulted in three cancer biomodules. Survival analysis revealed that the embryonic developmental biomodule centered on homeobox genes Meis1, Meis2 and Pbx1 to have clinical import. This homeobox biomodule detected a survival difference in a set of active surveillance patients (n=172, p=0.05) and identified men who were more likely to recur biochemically post-prostatectomy (n=78, p=0.02). We analyzed in vitro protein expression of Meis1, Meis2, Pbx1 and confirmed decreased gene expression in independent datasets of prostate cancer versus normal tissue. Conclusions: The Meis1/Meis2/Pbx1 biomodule may explain key differences in seminal vesicle and normal prostate epithelium development. In contrast to other cancers, Meis1, Meis2, and Pbx1 may play a tumor suppressor role in prostate cancer. Thus deregulation of this biomodule may be critical in prostate cancer oncogenesis.

scholarly journals Bioinformatics Analysis Reveals the Potential Diagnostic Biomarkers for Abdominal Aortic Aneurysm

2021 ◽  
Vol 8 ◽  
Author(s):  
Xinsheng Xie ◽  
En ci Wang ◽  
Dandan Xu ◽  
Xiaolong Shu ◽  
Yu fei Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Inflammatory Responses ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Aortic Aneurysms ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Abdominal Aortic

Objectives: Abdominal aortic aneurysms (AAAs) are associated with high mortality rates. The genes and pathways linked with AAA remain poorly understood. This study aimed to identify key differentially expressed genes (DEGs) linked to the progression of AAA using bioinformatics analysis.Methods: Gene expression profiles of the GSE47472 and GSE57691 datasets were acquired from the Gene Expression Omnibus (GEO) database. These datasets were merged and normalized using the “sva” R package, and DEGs were identified using the limma package in R. The functions of these DEGs were assessed using Cytoscape software. We analyzed the DEGs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Protein–protein interaction networks were assembled using Cytoscape, and crucial genes were identified using the Cytoscape plugin, molecular complex detection. Data from GSE15729 and GSE24342 were also extracted to verify our findings.Results: We found that 120 genes were differentially expressed in AAA. Genes associated with inflammatory responses and nuclear-transcribed mRNA catabolic process were clustered in two gene modules in AAA. The hub genes of the two modules were IL6, RPL21, and RPL7A. The expression levels of IL6 correlated positively with RPL7A and negatively with RPL21. The expression of RPL21 and RPL7A was downregulated, whereas that of IL6 was upregulated in AAA.Conclusions: The expression of RPL21 or RPL7A combined with IL6 has a diagnostic value for AAA. The novel DEGs and pathways identified herein might provide new insights into the underlying molecular mechanisms of AAA.

scholarly journals Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Cheng Zhang ◽  
Bingye Zhang ◽  
Di Meng ◽  
Chunlin Ge
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Ppi Networks ◽  
Differentially Methylated Genes ◽  
Tumorigenesis And Progression

Abstract Background The incidence of cholangiocarcinoma (CCA) has risen in recent years, and it has become a significant health burden worldwide. However, the mechanisms underlying tumorigenesis and progression of this disease remain largely unknown. An increasing number of studies have demonstrated crucial biological functions of epigenetic modifications, especially DNA methylation, in CCA. The present study aimed to identify and analyze methylation-regulated differentially expressed genes (MeDEGs) involved in CCA tumorigenesis and progression by bioinformatics analysis. Methods The gene expression profiling dataset (GSE119336) and gene methylation profiling dataset (GSE38860) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified using the limma packages of R and GEO2R, respectively. The MeDEGs were obtained by overlapping the DEGs and DMGs. Functional enrichment analyses of these genes were then carried out. Protein–protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape to determine hub genes. Finally, the results were verified based on The Cancer Genome Atlas (TCGA) database. Results We identified 98 hypermethylated, downregulated genes and 93 hypomethylated, upregulated genes after overlapping the DEGs and DMGs. These genes were mainly enriched in the biological processes of the cell cycle, nuclear division, xenobiotic metabolism, drug catabolism, and negative regulation of proteolysis. The top nine hub genes of the PPI network were F2, AHSG, RRM2, AURKB, CCNA2, TOP2A, BIRC5, PLK1, and ASPM. Moreover, the expression and methylation status of the hub genes were significantly altered in TCGA. Conclusions Our study identified novel methylation-regulated differentially expressed genes (MeDEGs) and explored their related pathways and functions in CCA, which may provide novel insights into a further understanding of methylation-mediated regulatory mechanisms in CCA.

scholarly journals Identification of regulatory factors promoting embryogenic callus formation in barley through transcriptome analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jingqi Suo ◽  
Chenlu Zhou ◽  
Zhanghui Zeng ◽  
Xipu Li ◽  
Hongwu Bian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transformation Efficiency ◽  
Callus Formation ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Differentially Expressed ◽  
Regulation Of Transcription ◽  
Growth Trend ◽  
Regulatory Factors

Abstract Background Barley is known to be recalcitrant to tissue culture, which hinders genetic transformation and its biotechnological application. To date, the ideal explant for transformation remains limited to immature embryos; the mechanism underlying embryonic callus formation is elusive. Results This study aimed to uncover the different transcription regulation pathways between calli formed from immature (IME) and mature (ME) embryos through transcriptome sequencing. We showed that incubation of embryos in an auxin-rich medium caused dramatic changes in gene expression profiles within 48 h. Overall, 9330 and 11,318 differentially expressed genes (DEGs) were found in the IME and ME systems, respectively. 3880 DEGs were found to be specific to IME_0h/IME_48h, and protein phosphorylation, regulation of transcription, and oxidative-reduction processes were the most common gene ontology categories of this group. Twenty-three IAA, fourteen ARF, eight SAUR, three YUC, and four PIN genes were found to be differentially expressed during callus formation. The effect of callus-inducing medium (CIM) on IAA genes was broader in the IME system than in the ME system, indicating that auxin response participates in regulating cell reprogramming during callus formation. BBM, LEC1, and PLT2 exhibited a significant increase in expression levels in the IME system but were not activated in the ME system. WUS showed a more substantial growth trend in the IME system than in the ME system, suggesting that these embryonic, shoot, and root meristem genes play crucial roles in determining the acquisition of competency. Moreover, epigenetic regulators, including SUVH3A, SUVH2A, and HDA19B/703, exhibited differential expression patterns between the two induction systems, indicating that epigenetic reprogramming might contribute to gene expression activation/suppression in this process. Furthermore, we examined the effect of ectopic expression of HvBBM and HvWUS on Agrobacterium-mediated barley transformation. The transformation efficiency in the group expressing the PLTPpro:HvBBM + Axig1pro:HvWUS construct was increased by three times that in the control (empty vector) because of enhanced plant regeneration capacity. Conclusions We identified some regulatory factors that might contribute to the differential responses of the two explants to callus induction and provide a promising strategy to improve transformation efficiency in barley.

Transcriptomal analysis of failing and nonfailing human hearts

2003 ◽  
Vol 12 (2) ◽  
pp. 97-112 ◽  
Author(s):  
M. Steenman ◽  
Y.-W. Chen ◽  
M. Le Cunff ◽  
G. Lamirault ◽  
A. Varró ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiac Function ◽  
Expression Profile ◽  
Large Scale ◽  
Expression Profiles ◽  
Statistical Tests ◽  
Differentially Expressed ◽  
Developmental Gene Expression ◽  
Similar Expression Profile

Heart failure is a multifactorial disease that may result from different initiating events. To contribute to an improved comprehension of normal cardiac function and the molecular events leading to heart failure, we performed large-scale gene expression analysis of failing and nonfailing human ventricle. Our aim was to define and compare expression profiles of 4 specific pathophysiological cardiac situations: 1) left ventricle (LV) from nonfailing heart; 2) LV from failing hearts affected by dilated cardiomyopathy (DCM); 3) LV from failing hearts affected by ischemic CM (ICM); 4) right ventricle (RV) from failing hearts affected by DCM or ICM. We used oligonucleotide arrays representing ∼12,000 human genes. After stringent numerical analyses using several statistical tests, we identified 1,306 genes with a similar expression profile in all 4 cardiac situations, therefore representative of part of the human cardiac expression profile. A total of 95 genes displayed differential expression between failing and nonfailing heart samples, reflecting a reversal to developmental gene expression, dedifferentiation of failing cardiomyocytes, and involvement of apoptosis. Twenty genes were differentially expressed between failing LV and failing RV, identifying possible candidates for different functioning of both ventricles. Finally, no genes were found to be significantly differentially expressed between failing DCM and failing ICM LV, emphasizing that transcriptomal analysis of explanted hearts results mainly in identification of expression profiles of end-stage heart failure and less in determination of expression profiles of the underlying etiology. Taken together, our data resulted in identification of putative transcriptomal landmarks for normal and disturbed cardiac function.

scholarly journals Identification of Regulatory Factors Promoting Embryogenic Callus Formation in Barley Through Transcriptome Analysis

2020 ◽  
Author(s):  
Jingqi Suo ◽  
Chenlu Zhou ◽  
Zhanghui Zeng ◽  
Xipu Li ◽  
Hongwu Bian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transformation Efficiency ◽  
Callus Formation ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Immature Embryo ◽  
Differentially Expressed ◽  
Regulation Of Transcription ◽  
Growth Trend ◽  
Regulatory Factors

Abstract Background: Barley is known to be recalcitrant to tissue culture, which hinders genetic transformation and its biotechnological application. To date, the ideal explant for transformation is still limited to immature embryos; however, the mechanism underlying embryonic callus formation remains elusive.Results: The aim of this study was to uncover the differential transcription regulation pathways between immature embryo (IME)- and mature embryo (ME)-derived callus formation through transcriptome sequencing. We showed that incubation of embryos on auxin-rich medium caused dramatic changes in gene expression profiles within 48 h. A total of 9330 and 11318 differentially expressed genes (DEGs) were found in the IME and ME systems, respectively. Protein phosphorylation, regulation of transcription, and oxidative-reduction process were the most common gene ontology categories of DEGs specific to the IME system. Twenty-three IAA, 14 ARF, 8 SAUR, 3 YUC, and 4 PIN genes were found to be differentially expressed during callus formation. The effect of callus-inducing medium (CIM) on IAA genes was broader in the IME system than in the IM system, indicating that auxin response and transport cooperate in regulating cell reprogramming during callus formation. BBM, LEC1 and PLT2 exhibited a significant increase in expression level during IME system but were not activated in the ME system, WUS showed a more substantial growth trend in the IME system than in the ME system, suggesting that these embryonic, shoot, and root meristems genes play crucial roles in determining the acquisition of competency. In addition, epigenetic regulators—including SUVH3A, SUVH2A, HDA19B/703—exhibited differential expression patterns between the two induction systems, indicating that epigenetic reprogramming might contribute to gene expression activation/suppression in this process. Furthermore, we examined the effect of ectopic expression of HvBBM and HvWUS on Agrobacterium-mediated barley transformation. The transformation efficiency was increased by three times in the group expressing the PLTPpro:HvBBM +Axig1pro:HvWUS construct, compared to that in the control (empty vector), which was due to an enhancement of plant regeneration capacity. Conclusions: We identified some regulatory factors that might contribute to the differential responses of the two explants to callus induction and provide a promising strategy to improve transformation efficiency in barley.

scholarly journals Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations

2021 ◽  
Vol 14 (10) ◽  
pp. 999
Author(s):  
Alexander Panossian ◽  
Sara Abdelfatah ◽  
Thomas Efferth
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Network Pharmacology ◽  
Pharmacokinetic Studies ◽  
Red Ginseng ◽  
Toxic Concentration ◽  
Wide Range ◽  
Ginsenoside Rg5

Numerous in vitro studies on isolated cells have been conducted to uncover the molecular mechanisms of action of Panax ginseng Meyer root extracts and purified ginsenosides. However, the concentrations of ginsenosides and the extracts used in these studies were much higher than those detected in pharmacokinetic studies in humans and animals orally administered with ginseng preparations at therapeutic doses. Our study aimed to assess: (a) the effects of ginsenoside Rg5, the major “rare” ginsenoside of Red Ginseng, on gene expression in the murine neuronal cell line HT22 in a wide range of concentrations, from 10−4 to 10−18 M, and (b) the effects of differentially expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in HT22 cells after treatment with ginsenoside Rg5. Ginsenoside Rg5 exhibits soft-acting effects on gene expression of neuronal cells in a wide range of physiological concentrations and strong reversal impact at high (toxic) concentration: significant up- or downregulation of expression of about 300 genes at concentrations from 10−6 M to 10−18 M, and dramatically increased both the number of differentially expressed target genes (up to 1670) and the extent of their expression (fold changes compared to unexposed cells) at a toxic concentration of 10−4 M. Network pharmacology analyses of genes’ expression profiles using ingenuity pathway analysis (IPA) software showed that at low physiological concentrations, ginsenoside Rg5 has the potential to activate the biosynthesis of cholesterol and to exhibit predictable effects in senescence, neuroinflammation, apoptosis, and immune response, suggesting soft-acting, beneficial effects on organismal death, movement disorders, and cancer.

scholarly journals Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations

2021 ◽  
Author(s):  
Alexander Panossian ◽  
Sara Abdelfatah ◽  
Thomas Efferth
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Network Pharmacology ◽  
Pharmacokinetic Studies ◽  
Red Ginseng ◽  
Toxic Concentration ◽  
Wide Range ◽  
Ginsenoside Rg5

Numerous in vitro studies on isolated cells have been conducted to uncover the molecular mechanisms of action of Panax ginseng Meyer root extracts and purified ginsenosides. However, the concentrations of ginsenosides and the extracts used in these studies were much higher than detected in pharmacokinetic studies in humans and animals orally administered with ginseng preparations at therapeutic doses. Our study aimed to assess: (a) the effects of ginsenoside Rg5, the major "rare" ginsenoside of Red Ginseng, on gene expression in the murine neuronal cell line HT22 in a wide range of concentrations, from 10-4 to 10-18 M, and (b) the effects of differentially expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in HT22 cells after treatment with ginsenoside Rg5. Ginsenoside Rg5 exhibits soft-acting effects on gene expression of neuronal cells in a wide range of physiological concentrations and strong reversal impact at high (toxic) concentration: significant up- or downregulation of expression of about 300 genes at concentrations from 10-6 M to 10-18 M, and dramatically increased both the number of differentially expressed target genes (up to 1670) and the extent of their expression (fold changes compared to unexposed cells) at a toxic concentration of 10-4 M. Network pharmacology analyses of genes expression profiles using Ingenuity pathway analysis (IPA) software showed that at low physiological concentrations, ginsenoside Rg5 has the potential to activate the biosynthesis of cholesterol and to exhibit predictable effects in senescence, neuroinflammation, apoptosis, and immune response, suggesting soft-acting, beneficial effects on organismal death, movement disorders, and cancer.

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