scholarly journals Integrated Strategy of UHPLC-Q-TOF-MS and Molecular Networking for Identification of Diterpenoids from Euphorbia fischeriana Steud. and Prediction of the Anti-Breast-Cancer Mechanism by the Network Pharmacological Method

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Tian-Cheng Ma ◽  
Yu-Kun Ma ◽  
Jin-Ling Zhang ◽  
Lei Liu ◽  
Jia Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Complementary Therapy ◽  
Mapk Signaling ◽  
Pathway Enrichment Analysis ◽  
Molecular Networking ◽  
Docking Simulations ◽  
Integrated Strategy ◽  
Euphorbia Fischeriana ◽  
Tof Ms

Breast cancer is one of the most common malignancies in women worldwide. Traditional Chinese medicine has been used as adjunctive or complementary therapy for breast cancer. Diterpenoids from Euphorbia fischeriana Steud. have been demonstrated to possess anti-breast-cancer activity. This research was aimed to systematically explore the diterpenoids from E. fischeriana and study the multiple mechanisms on breast cancer. The structures of diterpenoids were identified by the integrated strategy of UHPLC-Q-TOF-MS and molecular networking. A total of 177 diterpenoids belonging to 13 types were collected. In silico ADME analysis was performed on these compounds. It indicated that 130 of 177 diterpenoids completely adjusted to Lipinski’s rule. The targets of compounds were obtained from PharmMapper. The targets of breast cancer were collected from GeneCards. Then, 197 compounds-related targets and 544 breast cancer-related targets were identified. After the intersection process, 58 overlapping targets between compounds-related targets and breast cancer-related targets were acquired. The STRING database was applied to predict the protein-protein interactions. The GO and KEGG pathway enrichment analysis were performed by using the KOBAS database. It indicated that these predicted pathways were closely related to breast cancer. The treatment effect of E. fischeriana on breast cancer might be performed through signaling pathways, such as IL-17 signaling pathway, MAPK signaling pathway, and PI3K-Akt signaling pathway. The predicted top genes such as EGFR, ESR, MAPK, SRC, CASP3, CDK2, and KDR were involved in cell proliferation, gene transcription, apoptosis, signal transduction, DNA damage and repair, tumor differentiation, metastasis, and cell cycle, which indicated that E. fischeriana might treat breast cancer comprehensively. A compounds-KEGG pathways-related targets network was built by using cytoHubba to analyze the hub compounds and targets. It concluded that E. fischeriana treated breast cancer not only by the main components but also by the microconstituents, which reflected the overall regulatory role of multicomponents treating breast cancer. To estimate the binding affinities, binding sites, and binding postures, molecular docking simulations between 177 diterpenoids and top 19 targets were carried out. The results are basically in line with expectations. In conclusion, these results can serve as references for researchers studying potential targets of diterpenoids from E. fischeriana on breast cancer in the future.

scholarly journals Chemical Characteristics of Platycodon grandiflorum and its Mechanism in Lung Cancer Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Yaling Deng ◽  
Xianwen Ye ◽  
Yufan Chen ◽  
Hongmin Ren ◽  
Lanting Xia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Topological Analysis ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Triterpenoid Saponins ◽  
Platycodon Grandiflorum ◽  
Tof Ms

Objective: The technology, network pharmacology and molecular docking technology of the ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to explore the potential molecular mechanism of Platycodon grandiflorum (PG) in the treatment of lung cancer (LC).Methods: UPLC-Q-TOF-MS/MS technology was used to analyze the ingredients of PG and the potential LC targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database, and the Analysis Platform (TCMSP), GeneCards and other databases. The interaction network of the drug-disease targets was constructed with the additional use of STRING 11.0. The pathway enrichment analysis was carried out using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) in Metascape, and then the “Drug-Ingredients-Targets-Pathways-Disease” (D-I-T-P-D) network was constructed using Cytoscape v3.7.1. Finally, the Discovery Studio 2016 (DS) software was used to evaluate the molecular docking.Results: Forty-seven compounds in PG, including triterpenoid saponins, steroidal saponins and flavonoids, were identified and nine main bioactive components including platycodin D were screened. According to the method of data mining, 545 potential drug targets and 2,664 disease-related targets were collected. The results of topological analysis revealed 20 core targets including caspase 3 (CASP3) and prostaglandin-endoperoxide synthase 2 (PTGS2) suggesting that the potential signaling pathway potentially involved in the treatment of LC included MAPK signaling pathway and P13K-AKT signaling pathway. The results of molecular docking proved that the bound of the ingredients with potential key targets was excellent.Conclusion: The results in this study provided a novel insight in the exploration of the mechanism of action of PG against LC.

scholarly journals CILP Inhibits Brain Metastasis by Meditating Mast Cells via the MAPK Signaling Pathway in Breast Cancer

2021 ◽  
Author(s):  
Xiaolin Sun ◽  
Xingguo Zhou ◽  
Alei Feng ◽  
Gongwen Xu ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mast Cells ◽  
Correlation Analysis ◽  
Brain Metastases ◽  
Signaling Pathway ◽  
Immune Cells ◽  
Cell Activity ◽  
Mapk Signaling ◽  
High Morbidity ◽  
Spearman’S Correlation

Abstract Background: Approximately 15–30% of patients with breast cancer (BRCA) eventually develop brain metastases (BMs) with high morbidity and mortality. Herein, we aimed to identify genes specific to breast cancer brain metastases (BCBM) from an immune infiltration perspective.Methods: GSE100534 and GSE125989 were obtained from the NCBI Gene Expression Omnibus (GEO), then performed normalization using Rstudio and perl 5. We constructed a Weighted Gene Co-Expression Network Analysis (WGCNA) and obtained differentially expressed genes (DEGs) in BMs sample compared with primary BRCA tissue. Then we performed GO and KEGG pathway analysis. The LinkedOmics and UALCAN analysis showed the expression of gene in BRCA. The Kaplan-Meier plotter database was used to evaluate the prognosis. The composition of significant tumor-infiltrating immune cells was assessed using the CIBERSORT algorithm. Spearman’s correlation analysis revealed the correlation between CILP gene and immune cells in TCGA cohort and Timer database. Using GSEA analysis, we conducted to identify the potential pathways in BCBM.Results: The cartilage intermediate layer protein (CILP) was a late event in BRCA (stage III to IV) with poor prognosis (P< 0.05). LinkedOmics showed that the mRNA expression of CILP was down-regulated in advanced cancer (P< 0.05). Besides, UALCAN analysis showed that CILP expression was downregulated in HER2-positive and triple-negative breast cancer which were more prone to BMs (P< 0.05). CILP was the hub gene which was significantly associated with BCBM identified by WGCNA (R2=−0.6, P=3e-06). We found that the resting infiltration of mast cells in the BCBM group was significantly lower than that in the primary BRCA group (P= 0.01). In addition, Spearman’s correlation analysis revealed that the expression of CILP positively correlated with that of mast cells (P< 0.05). Finally, the FCERI-mediated MAPK activation (NES=2.1847, P=0, FDR=0.0031), which could regulate mast cell activity, were enriched in BCBM.Conclusions: CILP can influence the progression of BRCA favored for BMs through meditating mast cells via the MAPK signaling pathway.

scholarly journals Anticancer Effects of Emodin on HepG2 Cell: Evidence from Bioinformatic Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Rui-sheng Zhou ◽  
Xiong-Wen Wang ◽  
Qin-feng Sun ◽  
Zeng Jie Ye ◽  
Jian-wei Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Ion Concentration ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Mrna Levels ◽  
Hub Genes ◽  
Positive Regulation

Hepatocellular carcinoma (HCC) is a primary cause of cancer-related death in the world. Despite the fact that there are many methods to treat HCC, the 5-year survival rate of HCC is still at a low level. Emodin can inhibit the growth of HCC cells invitroand invivo. However, the gene regulation of emodin in HCC has not been well studied. In our research, RNA sequencing technology was used to identify the differentially expressed genes (DEGs) in HepG2 cells induced by emodin. A total of 859 DEGs were identified, including 712 downregulated genes and 147 upregulated genes in HepG2 cells treated with emodin. We used DAVID for function and pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed using STRING, and Cytoscape was used for module analysis. The enriched functions and pathways of the DEGs include positive regulation of apoptotic process, structural molecule activity and lipopolysaccharide binding, protein digestion and absorption, ECM-receptor interaction, complement and coagulation cascades, and MAPK signaling pathway. 25 hub genes were identified and pathway analysis revealed that these genes were mainly enriched in neuropeptide signaling pathway, inflammatory response, and positive regulation of cytosolic calcium ion concentration. Survival analysis showed that LPAR6, C5, SSTR5, GPR68, and P2RY4 may be involved in the molecular mechanisms of emodin therapy for HCC. A quantitative real-time PCR (qRT-PCR) assay showed that the mRNA levels of LPAR6, C5, SSTR5, GPR68, and P2RY4 were significantly decreased in HepG2 cells treated with emodin. In conclusion, the identified DEGs and hub genes in the present study provide new clues for further researches on the molecular mechanisms of emodin.

scholarly journals Anti-Breast Cancer Effect of 2-Dodecyl-6-Methoxycyclohexa-2,5-Diene-1,4-Dione in vivo and in vitro Through MAPK Signaling Pathway

2020 ◽  
Vol Volume 14 ◽  
pp. 2667-2684 ◽  
Author(s):  
Xing Zhou ◽  
Xingchun Wu ◽  
Luhui Qin ◽  
Shunyu Lu ◽  
Hongliang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

scholarly journals miR-3188 Regulates Cell Proliferation, Apoptosis, and Migration in Breast Cancer by Targeting TUSC5 and Regulating the p38 MAPK Signaling Pathway

2018 ◽  
Vol 26 (3) ◽  
pp. 363-372 ◽  
Author(s):  
Xiaowen Chen ◽  
Jianli Chen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Luciferase Reporter ◽  
And Migration ◽  
Mcf 7

This study intended to investigate the effects of miR-3188 on breast cancer and to reveal the possible molecular mechanisms. miR-3188 was upregulated and TUSC5 was downregulated in breast cancer tissues and MCF-7 cells compared to normal tissue and MCF-10 cells. After MCF-7 cells were transfected with miR-3188 inhibitor, cell proliferation and migration were inhibited, whereas apoptosis was promoted. Luciferase reporter assay suggested that TUSC5 was a target gene of miR-3188. In addition, miR-3188 overexpression increased the p-p38 expression, while miR-3188 suppression decreased the p-p38 expression significantly. miR-3188 regulated breast cancer progression via the p38 MAPK signaling pathway. In conclusion, miR-3188 affects breast cancer cell proliferation, apoptosis, and migration by targeting TUSC5 and activating the p38 MAPK signaling pathway. miR-3188 may serve as a potential therapeutic agent for the treatment of breast cancer.

scholarly journals Comprehensive circRNA Expression Profile and Construction of circRNAs-Related ceRNA Network in a Mouse Model of Autism

2021 ◽  
Vol 11 ◽  
Author(s):  
Ji Wang ◽  
Zhongxiu Yang ◽  
Canming Chen ◽  
Yang Xu ◽  
Hongguang Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Expression Profile ◽  
Enrichment Analysis ◽  
Notch Signaling Pathway ◽  
Mapk Signaling ◽  
Circular Rnas ◽  
Pathway Enrichment Analysis ◽  
Common Disease ◽  
Cerna Network

Autism is a common disease that seriously affects the quality of life. The role of circular RNAs (circRNAs) in autism remains largely unexplored. We aimed to detect the circRNA expression profile and construct a circRNA-based competing endogenous RNA (ceRNA) network in autism. Valproate acid was used to establish an in vivo model of autism in mice. A total of 1,059 differentially expressed circRNAs (477 upregulated and 582 downregulated) in autism group was identified by RNA sequencing. The expression of novel_circ_015779 and novel_circ_035247 were detected by real-time PCR. A ceRNA network based on altered circRNAs was established, with 9,715 nodes and 150,408 edges. Module analysis was conducted followed by GO and KEGG pathway enrichment analysis. The top three modules were all correlated with autism-related pathways involving “TGF-beta signaling pathway,” “Notch signaling pathway,” “MAPK signaling pathway,” “long term depression,” “thyroid hormone signaling pathway,” etc. The present study reveals a novel circRNA involved mechanisms in the pathogenesis of autism.

scholarly journals miR-130b Acts as an Oncogene and Prognostic Biomarker of Breast Cancer: A Bioinformatic Analysis

2020 ◽  
Author(s):  
Xinyue Chen ◽  
Lijun Hao
Keyword(s):  
Breast Cancer ◽  
Thyroid Hormone ◽  
Signaling Pathway ◽  
Target Genes ◽  
Kegg Pathway ◽  
Prognostic Biomarker ◽  
Pathway Enrichment Analysis ◽  
Hormone Signaling ◽  
Ppi Network ◽  
Hub Genes

Abstract Background: Breast cancer (BC) is the most prevalent cancer among females globally. microRNAs (miRNAs) could regulate the expression levels of cancer-related genes through binding with target mRNAs. In various cancers, the abnormal expression of miR-130b has been detected. We aims to investigate the molecular mechanism and biological function of miR130b in breast cancer.Methods: We obtained two microRNA expression profiles from the Gene Expression Omnibus (GEO) database, including GSE45666 and GSE26659. We identified differentially expressed miRNAs (DE-miRNAs) between BC tissue and normal breast tissue based on the GEO2R web tool. DE-miRNAs were filtered by significant prognostic value resulting from Kaplan–Meier plotter. We used the JASPAR database to explore upstream regulators of miR-130b. The potential molecular mechanisms of miR-130b correlation genes were revealed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis in WebGestalt. Protein–protein interaction (PPI) network of miR-130b target genes was constructed by STRING. Cytoscape software was used to visualize the PPI network and hub genes.Results: miR-130b was highly expressed in breast cancer tissues, which positively correlates with poor prognostic. JASPAR revealed THAP11 might be the upstream regulator of miR-130b. In addition, GO, and KEGG pathway revealed that miR-130b positively regulated PFKP, STAT1, SRC, and NOTCH2, participating in the Thyroid hormone signaling pathway. The PPI network further identified that AR, KIT, and ESR1 as hub genes in BC development.Conclusion: miR-130b, which is regulated by THAP11, acts as an oncogene and prognostic biomarker in BC by mediating the Thyroid hormone signaling pathway and potential target genes. miR-130b might be a novel therapeutic target for BC treatment.

scholarly journals Uncovering the Mechanisms and Molecular Targets of Weibing Formula 1 against Gastritis: Coupling Network Pharmacology with GEO Database

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Ke Chen ◽  
Luojian Zhang ◽  
Zhen Qu ◽  
Feng Wan ◽  
Jia Li ◽  
...  
Keyword(s):  
Real Time ◽  
Signaling Pathway ◽  
Quantitative Pcr ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Gene Expression Omnibus ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Real Time Quantitative Pcr

Weibing Formula 1, a classic traditional formula, has been widely used clinically to treat gastritis in recent years. However, the potential pharmacological mechanism of Weibing Formula 1 is still unclear to date. A network pharmacology-based strategy was performed to uncover the underlying mechanisms of Weibing Formula 1 against gastritis. Furthermore, we structured the drug-active ingredients-genes–disease network and PPI network of shared targets, and function enrichment analysis of these targets was carried out. Ultimately, Gene Expression Omnibus (GEO) datasets and real-time quantitative PCR were used to verify the related genes. We found 251 potential targets corresponding to 135 bioactive components of Weibing Formula 1. Then, 327 gastritis-related targets were known gastritis-related targets. Among which, 60 common targets were shared between potential targets of Weibing Formula 1 and known gastritis-related targets. The results of pathway enrichment analysis displayed that 60 common targets mostly participated in various pathways related to Toll-like receptor signaling pathway, MAPK signaling pathway, cytokine-cytokine receptor interaction pathway, chemokine signaling pathway, and apoptosis. Based on the GSE60427 dataset, 15 common genes were shared between differentially expressed genes and 60 candidate targets. The verification results of the GSE5081 dataset showed that except for DUOX2 and VCAM1, the other 13 genes were significantly upregulated in gastritis, which was consistent with the results in the GSE60427 dataset. More importantly, real-time quantitative PCR results showed that the expressions of PTGS2, MMP9, CXCL2, and CXCL8 were significantly upregulated and NOS2, EGFR, and IL-10 were downregulated in gastritis patients, while the expressions of PTGS2, MMP9, CXCL2, and CXCL8 were significantly downregulated and NOS2, EGFR, and IL-10 were upregulated after the treatment of Weibing Formula 1. PTGS2, NOS2, EGFR, MMP9, CXCL2, CXCL8, and IL-10 may be the important direct targets of Weibing Formula 1 in gastritis treatment. Our study revealed the mechanism of Weibing Formula 1 in gastritis from an overall and systematic perspective, providing a theoretical basis for further knowing and application of this formula in the future.

scholarly journals RNA-binding protein QKI suppresses breast cancer via RASA1/MAPK signaling pathway

2021 ◽  
Vol 9 (2) ◽  
pp. 104-104
Author(s):  
Yun Cao ◽  
Chengyu Chu ◽  
Xiaoyan Li ◽  
Siwen Gu ◽  
Qiang Zou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway
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