scholarly journals Systematically Exploring the Antitumor Mechanisms of Core Chinese Herbs on Hepatocellular Carcinoma: A Computational Study

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhulin Wu ◽  
Li He ◽  
Lianan Wang ◽  
Lisheng Peng

Objective. Chinese herbs play a positive role in the management of hepatocellular carcinoma (HCC) in China. However, it is not clear which of Chinese herbs are critical for the treatment of HCC. Besides, mechanisms of CCHs in the treatment of HCC remain unclear. Hence, our goal is to identify the core Chinese herbs (CCHs) for treating HCC and explore their antitumor mechanism. Methods. Firstly, clinical traditional Chinese medicine (TCM) prescriptions for HCC were collected from Chinese National Knowledge Infrastructure (CNKI) database, and then, data mining software was used to identify CCHs. After that, bioactive compounds and corresponding target genes of CCHs were obtained using three TCM databases, and target genes of HCC were acquired from MalaCards and OMIM. Subsequently, common target genes of CCHs and HCC were screened. Moreover, biological functions and pathways were analyzed, and Cytoscape plugin cytoHubba was used to identify hub genes. Finally, prognostic values of hub genes were verified by survival analysis, and the molecular docking approach was utilized to validate the interactions between targets and bioactive compounds of CCHs. Results. Eight CCHs were determined from 630 prescriptions, and 100 bioactive compounds (e.g., quercetin and luteolin) and 126 common target genes were screened. Furthermore, common target genes of CCHs and HCC were mainly enriched in cancer-associated pathways, and six hub genes with statistical significance in survival analysis were selected as key target genes for molecular docking. Additionally, molecular docking showed that the bioactive compounds docked well with the protein receptors of key target genes. Conclusion. By combining data mining, network pharmacology, molecular docking, and survival analysis methods, we found that CCHs may play a therapeutic role in HCC through regulating the target genes and pathways related to cancer occurrence and development, angiogenesis, metastasis, and prognosis.

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Tong Lin ◽  
Caijun Liang ◽  
Wenya Peng ◽  
Yuqin Qiu ◽  
Lisheng Peng

Colorectal cancer (CRC) is now the second most deadly cancer globally. Chinese herbal medicine (CHM) plays an indispensable role in CRC treatment in China. However, the core herbs (the CHs) in the treatment of CRC and their underlying therapeutic mechanisms remain unclear. This study aims to uncovering the CHs and their mechanisms of action of CRC treatment, applying data mining and network pharmacology approach. First, CHM prescriptions treating CRC were collected from clinical studies from the Chinese National Knowledge Infrastructure (CNKI) and MEDLINE databases, and the CHs were identified through data mining. Then, the bioactive compounds and the corresponding putative targets of the CHs were obtained from three traditional Chinese medicine (TCM) databases. CRC related targets were acquired from three disease databases; the overlapping targets between the CHs and CRC were identified as the therapeutic targets. Subsequently, functional enrichment analysis was performed to elucidate the mechanisms of the CHs on CRC. Moreover, networks were constructed to screen the major bioactive compounds and therapeutic targets. Finally, prognostic values of the major target genes were evaluated by survival analysis, and molecular docking simulation was performed to assess the binding affinity of key targets and major bioactive compounds. It came out that 10 the CHs from 113 prescriptions and 190 bioactive compounds with 118 therapeutic targets were identified. The therapeutic targets were mainly enriched in the biological progress of transcription, apoptosis, and response to cytokine. Various cancer-associated signaling pathways, including microRNAs, TNF, apoptosis, PI3K-Akt, and p53, were involved. Furthermore, 15 major bioactive compounds and five key target genes (VEGFA, CASP3, MYC, CYP1Y1, and NFKB1) with prognostic significance were identified. Additionally, most major bioactive compounds might bind firmly to the key target proteins. This study provided an overview of the anti-CRC mechanisms of the CHs, which might refer to the regulation of apoptosis, transcription, and inflammation.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Rongjie Zhang ◽  
Yan Chen ◽  
Ge Zhou ◽  
Baoguo Sun ◽  
Yue Li ◽  
...  

Objectives. The purpose of this study was to identify the molecular mechanism and prognosis-related genes of Jianpi Jiedu decoction in the treatment of hepatocellular carcinoma. Methods. The gene expression data of hepatocellular carcinoma samples and normal tissue samples were downloaded from TCGA database, and the potential targets of drug composition of Jianpi Jiedu decoction were obtained from TCMSP database. The genes were screened out in order to obtain the expression of these target genes in patients with hepatocellular carcinoma. The differential expression of target genes was analyzed by R software, and the genes related to prognosis were screened by univariate Cox regression analysis. Then, the LASSO model was constructed for risk assessment and survival analysis between different risk groups. At the same time, independent prognostic analysis, GSEA analysis, and prognostic analysis of single gene in patients with hepatocellular carcinoma were performed. Results. 174 compounds of traditional Chinese medicine were screened by TCMSP database, corresponding to 122 potential targets. 39 upregulated genes and 9 downregulated genes were screened out. A total of 20 candidate prognostic related genes were screened out by univariate Cox analysis, of which 12 prognostic genes were involved in the construction of the LASSO regression model. There was a significant difference in survival time between the high-risk group and low-risk group ( p < 0.05 ). Among the genes related to prognosis, the expression levels of CCNB1, NQO1, NUF2, and CHEK1 were high in tumor tissues ( p < 0.05 ). Survival analysis showed that the high expression levels of these four genes were significantly correlated with poor prognosis of HCC ( p < 0.05 ). GSEA analysis showed that the main KEGG enrichment pathways were lysine degradation, folate carbon pool, citrate cycle, and transcription factors. Conclusions. In the study, we found that therapy target genes of Jianpi Jiedu decoction were mainly involved in metabolism and apoptosis in hepatocellular carcinoma, and there was a close relationship between the prognosis of hepatocellular carcinoma and the genes of CCNB1, NQO1, NUF2, and CHEK1.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhulin Wu ◽  
Lina Yang ◽  
Li He ◽  
Lianan Wang ◽  
Lisheng Peng

Objective. In this study, the data mining method was used to screen the core Chinese materia medicas (CCMMs) against primary liver cancer (PLC), and the potential mechanisms of CCMMs in treating PLC were analyzed based on network pharmacology. Methods. Traditional Chinese medicine (TCM) prescriptions for treating PLC were obtained from a famous TCM doctor in Shenzhen, China. According to the data mining technique, the TCM Inheritance Support System (TCMISS) was applied to excavate the CCMMs in the prescriptions. Then, bioactive ingredients and corresponding targets of CCMMs were collected using three different TCM online databases, and target genes of PLC were obtained from GeneCards and OMIM. Afterwards, common targets of CCMMs and PLC were screened. Furthermore, a network of CCMMs bioactive ingredients and common target gene was constructed by Cytoscape 3.7.1, and gene ontology (GO) and signaling pathways analyses were performed to explain the mechanism of CCMMs in treating PLC. Besides, protein-protein interaction (PPI) analysis was used to identify key target genes of CCMMs, and the prognostic value of key target genes was verified using survival analysis. Results. A total of 15 high-frequency Chinese materia medica combinations were found, and CCMMs (including Paeoniae Radix Alba, Radix Bupleuri, Macrocephalae Rhizoma, Coicis Semen, Poria, and Curcumae Radix) were identified by TCMISS. A total of 40 bioactive ingredients (e.g., quercetin, kaempferol, and naringenin) of CCMMs were obtained, and 202 common target genes of CCMMs and PLC were screened. GO analysis indicated that biological processes of CCMMs were mainly involved in response to drug, response to ethanol, etc. Pathway analysis demonstrated that CCMMs exerted its antitumor effects by acting on multiple signaling pathways, including PI3K-Akt, TNF, and MAPK pathways. Also, some key target genes of CCMMs were determined by PPI analysis, and four genes (MAPK3, VEGFA, EGF, and EGFR) were found to be correlated with survival in PLC patients. Conclusion. Based on data mining and network pharmacology methods, our results showed that the therapeutic effect of CCMMs on PLC may be realized by acting on multitargets and multipathways related to the occurrence and development of PLC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fan Zhang ◽  
Mengjuan Xue ◽  
Xin Jiang ◽  
Huiyuan Yu ◽  
Yixuan Qiu ◽  
...  

Abstract Background The incidence and mortality rates of hepatocellular carcinoma are among the highest of all cancers all over the world. However the survival rates are relatively low due to lack of effective treatments. Efforts to elucidate the mechanisms of HCC and to find novel prognostic markers and therapeutic targets are ongoing. Here we tried to identify prognostic genes of HCC through co-expression network analysis. Methods We conducted weighted gene co-expression network analysis with a microarray dataset GSE14520 of HCC from Gene Expression Omnibus database and identified a hub module associated with HCC prognosis. Function enrichment analysis of the hub module was performed. Clinical information was analyzed to select candidate hub genes. The expression profiles and survival analysis of the selected genes were performed using additional datasets (GSE45267 and TCGA-LIHC) and the hub gene was identified. GSEA and in vitro experiments were conducted to further verify the function of the hub gene. Results Genes in the hub module were mostly involved in the metabolism pathway. Four genes (SLC27A5, SLC10A1, PCK2 and FMO4) from the module were identified as candidate hub genes according to correlation analysis with prognostic indicators. All these genes were significantly down-regulated in tumor tissues compared with non-tumor tissues in additional datasets. After survival analysis and network construction, SLC27A5 was selected as a prognostic marker. GSEA analysis and in vitro assays suggested that SLC27A5 downregulation promoted tumor cell migration via enhancing epithelial-mesenchymal transition. Conclusion SLC27A5 is a potential biomarker of HCC and SLC27A5 downregulation promoted HCC progression by enhancing EMT.


2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Huang ◽  
Jinkun Lin ◽  
Surong Huang ◽  
Jianzhen Shen

Background: It has been verified that deficiency of Qi, a fundamental substance supporting daily activities according to the Traditional Chinese Medicine theory, is an important symptom of cancer. Qi-invigorating herbs can inhibit cancer development through promoting apoptosis and improving cancer microenvironment. In this study, we explored the potential mechanisms of Qi-invigorating herbs in diffuse large B cell lymphoma (DLBCL) through network pharmacology and in vitro experiment.Methods: Active ingredients of Qi-invigorating herbs were predicted from the Traditional Chinese Medicine Systems Pharmacology Database. Potential targets were obtained via the SwissTargetPrediction and STITCH databases. Target genes of DLBCL were obtained through the PubMed, the gene-disease associations and the Malacards databases. Overlapping genes between DLBCL and each Qi-invigorating herb were collected. Hub genes were subsequently screened via Cytoscape. The Gene Ontology and pathway enrichment analyses were performed using the DAVID database. Molecular docking was performed among active ingredients and hub genes. Hub genes linked with survival and tumor microenvironment were analyzed through the GEPIA 2.0 and TIMER 2.0 databases, respectively. Additionally, in vitro experiment was performed to verify the roles of common hub genes.Results: Through data mining, 14, 4, 22, 22, 35, 2, 36 genes were filtered as targets of Ginseng Radix et Rhizoma, Panacis Quinquefolii Radix, Codonopsis Radix, Pseudostellariae Radix, Astragali Radix, Dioscoreae Rhizoma, Glycyrrhizae Radix et Rhizoma for DLBCL treatment, respectively. Then besides Panacis Quinquefolii Radix and Dioscoreae Rhizoma, 1,14, 10, 14,13 hub genes were selected, respectively. Molecular docking studies indicated that active ingredients could stably bind to the pockets of hub proteins. CASP3, CDK1, AKT1 and MAPK3 were predicted as common hub genes. However, through experimental verification, only CASP3 was considered as the common target of Qi-invigorating herbs on DLBCL apoptosis. Furthermore, the TIMER2.0 database showed that Qi-invigorating herbs might act on DLBCL microenvironment through their target genes. Tumor-associated neutrophils may be main target cells of DLBCL treated by Qi-invigorating herbs.Conclusion: Our results support the effects of Qi-invigorating herbs on DLBCL. Hub genes and immune infiltrating cells provided the molecular basis for each Qi-invigorating herb acting on DLBCL.


2020 ◽  
Author(s):  
Jiayao Zhu ◽  
Yan Zhang ◽  
Jingjing Lu ◽  
Le Wang ◽  
Xiaoren Zhu ◽  
...  

Abstract Background: lung adenocarcinoma is the main subtype of lung cancer and the most fatal malignant disease in the world. However, the pathogenesis of lung adenocarcinoma has not been fully elucidated.Methods: Three LUAD-associated datesets (GSE118370, GSE43767 and GSE74190) were downloaded from the Gene Expression Omnibus (GEO) datebase and the differentially expressed miRNAs (DEMs) and genes (DEGs) were screened by GEO2R. The prediction of target gene of differentially expressed miRNA were used miRWALK. Metascape was used to enrich the overlapped genes of DEGs and target genes. Then, the protein-protein interaction(PPI) and DEMs-DEGs regulatory network were created via String datebase and Cytoscape. Finally, overall survival analysis was established via the Kaplan–Meier curve and look for the possible prognostic biomarkers.Result: In this study, 433 differential genes were identified. There were 267 genes overlapped with the target gene of Dems, and eight hub genes (CDH1, CDH5, CAV1, MMP9, PECAM1, CD24, ENG, MME) were screened out. There were 85 different miRNAs in total, among which 16 miRNA target genes intersect with DEGs, 12 miRNAs with the highest interaction were screened out, and survival analysis of miRNA and hub genes was carried out.Conclusion: we found that miRNA-940, miRNA-125a-3p, miRNA-140-3p, miRNA-542-5p, CDH1, CDH5, CAV1, MMP9, PECAM1 may be related to the development of LUAD.


2020 ◽  
Author(s):  
Ming Wu ◽  
Meijie Sang ◽  
Shuo Pan ◽  
Fei Liu ◽  
Meixiang Sang

Abstract Background Circular RNAs (circRNAs) have drawn lots of attention in tumorigenesis and progression. However, circRNAs as crucial regulators in multitudinous biological processes have not been systematically identified in breast cancer (BC). Our research aims to explore novel circRNAs in BC and their mechanisms of action. Methods The circRNA expression profile data, as well as RNA-sequencing data of BC, were downloaded from public database, respectively. The differentially expressed circRNAs, miRNA, and mRNA were determined via fold change filtering. The competing endogenous RNAs (ceRNAs) network were established on the foundation of the relationship between circular RNAs, miRNAs and mRNAs. GO and KEGG analysis of the overlapped genes were performed to predict the potential functions and mechanisms of circRNAs in BC. The CytoHubba was used to determine the hub genes from the PPI regulatory network. Morever, we further used Kaplan–Meier plotter to perform survival analysis of these hub genes. Real-time PCR was used to validate the expression of the circRNAs in BC tissues. Results A total of seven differential expressed circRNAs were screened. After the predicted target miRNA and DEmiRNA were intersected, four circRNA-miRNA interactions including three circRNAs and four miRNAs were determined. Furthermore, the Venn diagram was used to intersect the predicted target genes and the downregulated differentially expressed genes, and screened 149 overlapped genes. Moreover, we constructed a PPI network, and selecting six hub genes, including DGAT2, ACSL1, ADIPOQ, LPL, LEP, PCK1. Moreover, the survival analysis results revealed that low expression of ADIPOQ, LPL, LEP were obviously correlated with poor prognosis of BC patients. The real-time PCR results demonstrated that, the levels of circ_0028899, circ_0000375, and circ_0000376 were significantly down-regulated in breast cancer tissues. Conclusions Our study constructed and analyzed a circRNA-associated ceRNA regulatory network and discovered that circ_0028899, circ_0000375, and circ_0000376 may function as ceRNAs to serve key roles in BC.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Zhuomao Mo ◽  
Zhirui Cao ◽  
Ling Yu ◽  
Yongdan Wang ◽  
Pan Li ◽  
...  

Aims. Abundant evidences in traditional Chinese medicine (TCM) supported the therapeutic value of herbal medicine Yinchen in hepatocellular carcinoma (HCC), but the underlying mechanism remains to be investigated. Main Methods. The intersection of immune gene set, module genes, HCC-associated genes, and target genes of Yinchen was employed for further analyses. The module genes were identified by weighted gene coexpression network analysis, and the other three gene sets were obtained from public databases. Subsequently, we further explored the clinical value and immunoregulation of the hub gene of intersection. The relevant pathways related to hub gene expression were investigated by gene set enrichment analysis. Finally, the interaction of active compounds and target genes was validated by molecular docking. Key Findings. Thirteen active compounds and 90 target genes of Yinchen were included. After constructing the network among Yinchen, target genes, and HCC, BIRC5 was identified as the hub gene. Significant difference was found between the high-expressed group and the low-expressed group in survival and stage. Different immune subtypes also presented significant difference in BIRC5 expression. Moreover, NK cell and T cell (CD4+ effector memory and CD4+ memory resting) were negatively correlated with BIRC5 expression, while CTLA4 and LAG3 were positively correlated. The results of molecular docking further validated a good binding activity of quercetin-BIRC5 interaction. Significance. In summary, our research identified for the first time a novel underlying association among herbal medicine Yinchen, BIRC5, immunotherapy, and HCC. We speculated that Yinchen may target the immune checkpoints (CTLA4 and LAG3) and activate the immune cells by suppressing BIRC5.


2021 ◽  
Vol 12 ◽  
Author(s):  
Harish Joshi ◽  
Basavaraj Vastrad ◽  
Nidhi Joshi ◽  
Chanabasayya Vastrad ◽  
Anandkumar Tengli ◽  
...  

Obesity is an excess accumulation of body fat. Its progression rate has remained high in recent years. Therefore, the aim of this study was to diagnose important differentially expressed genes (DEGs) associated in its development, which may be used as novel biomarkers or potential therapeutic targets for obesity. The gene expression profile of E-MTAB-6728 was downloaded from the database. After screening DEGs in each ArrayExpress dataset, we further used the robust rank aggregation method to diagnose 876 significant DEGs including 438 up regulated and 438 down regulated genes. Functional enrichment analysis was performed. These DEGs were shown to be significantly enriched in different obesity related pathways and GO functions. Then protein–protein interaction network, target genes - miRNA regulatory network and target genes - TF regulatory network were constructed and analyzed. The module analysis was performed based on the whole PPI network. We finally filtered out STAT3, CORO1C, SERPINH1, MVP, ITGB5, PCM1, SIRT1, EEF1G, PTEN and RPS2 hub genes. Hub genes were validated by ICH analysis, receiver operating curve (ROC) analysis and RT-PCR. Finally a molecular docking study was performed to find small drug molecules. The robust DEGs linked with the development of obesity were screened through the expression profile, and integrated bioinformatics analysis was conducted. Our study provides reliable molecular biomarkers for screening and diagnosis, prognosis as well as novel therapeutic targets for obesity.


2020 ◽  
Author(s):  
Harish Joshi ◽  
Basavaraj Mallikarjunayya Vastrad ◽  
Nidhi Joshi ◽  
Anandkumar Tengli ◽  
Chanabasayya Mallikarjunayya Vastrad ◽  
...  

Abstract Obesity is the most common metabolic disorder worldwide. Its progression rate has remained high in recent years. Therefore, the aim of this study was to diagnose important differentially expressed genes (DEGs) associated in its development, which may be used as novel biomarkers or potential therapeutic targets for obesity. The gene expression profile of E-MTAB-6728 was downloaded from the database. After screening DEGs in each ArrayExpress dataset, we further used the robust rank aggregation method to diagnose 876 significant DEGs including 438 up regulated and 438 down regulated genes. Pathway enrichment analyses and Gene Ontology (GO) were performed by online tool ToppCluster. These DEGs were shown to be significantly enriched in different obesity related pathways and GO functions. Then, the mentha, miRNet and NetworkAnalyst databases were used to construct the protein–protein interaction network, target genes - miRNA regulatory network and target genes - TF regulatory network. The module analysis was performed by the PEWCC1 plug‐in of Cytoscape based on the whole PPI network. We finally filtered out HSPA8, ESR1, YWHAH, RPL14, SOD2, BTG2, LYZ and EFNA1 hub genes. Hub genes were validated by ICH analysis, Receiver operating curve (ROC) analysis and RT-PCR. Finally molecular docking study was performed. The robust DEGs linked with the development of obesity was screened through the ArrayExpress database, and integrated bioinformatics analysis was conducted. Our study provides reliable molecular biomarkers for screening and diagnosis, prognosis as well as novel therapeutic targets for obesity.


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