scholarly journals MicroRNA in Gastric Cancer Development: Mechanisms and Biomarkers

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 891
Author(s):  
Fatimat Kipkeeva ◽  
Tatyana Muzaffarova ◽  
Alexandra Korotaeva ◽  
Maxim Nikulin ◽  
Kristina Grishina ◽  
...  

Gastric cancer (GC) is one of the most common and difficult diseases to treat. The study of signaling pathway regulation by microRNA provides information on the mechanisms of GC development and is the basis for biomarker creation. In this study, a circuit of microRNA interactions with signaling pathways was constructed. The microRNAs, associated with metastasis and chemoresistance, are described. In most cases, microRNAs in GC regulate the Wnt/β-catenin, PI3K/AKT/mTOR, RAS/RAF/ERK/MAPK, NF-kB, TGF-β, and JAK/STAT pathways. Part of the microRNA acts on several target genes that function in different pathways. This often leads to an intensification of the induced processes. MicroRNAs have also been described that have the opposite effect on different pathways, causing different functional consequences. By acting on several target genes, or genes associated with several pathways, microRNAs can function in a signaling network. MicroRNAs associated with metastasis most often interact with the Wnt/β-catenin pathway. MicroRNAs affecting chemoresistance, in most cases, affect the regulators of apoptosis and are associated with the PI3K/AKT/mTOR pathway. The characteristics of microRNAs proposed as candidates for GC biomarkers were analyzed. The currently developed diagnostic and prognostic panels of microRNAs are also considered.

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Li Han ◽  
Ying Han

Background. Herba Sarcandrae is used in the clinical practice of traditional Chinese medicine to deal with gastric cancer. However, there are few studies on its precise mechanism. Method. In this study, a network pharmacological approach was utilized to construct a molecular/target/pathway molecular regulatory network for the anti-gastric-cancer effect of Herba Sarcandrae. The active components of Herba Sarcandrae and their potential mechanisms were explored. Chemical components of the Herba Sarcandrae were identified through a database, and they were evaluated and screened based on oral bioavailability and drug similarity. Results. Genes related to gastric cancer were found in the Gene Expression Omnibus (GEO) database, and gene targets related to anti-gastric-cancer were chosen by comparison. Using annotation, visualization, and a comprehensive discovery database, the function and related pathways of target genes were analyzed and screened. Cytoscape software was utilized to construct a component/target/pathway network for the antitumor effect of Herba Sarcandrae. Finally, 6 drug ingredients and 29 target genes related to gastric cancer were detected. IL-17 signaling pathway, NF-kappa B signaling pathway, and other signaling pathways were significantly enriched. Many signaling pathways that directly act on tumors and indirect pathways inhibit the development of gastric cancer. Conclusion. This study provides a scientific basis for further elucidating the mechanism of the anti-gastric-cancer effect of Herba Sarcandrae.


2020 ◽  
Vol 15 ◽  
Author(s):  
Yuan Gu ◽  
Ying Gao ◽  
Xiaodan Tang ◽  
Huizhong Xia ◽  
Kunhe Shi

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.


Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4787
Author(s):  
Katarzyna Papierska ◽  
Violetta Krajka-Kuźniak ◽  
Jarosław Paluszczak ◽  
Robert Kleszcz ◽  
Marcin Skalski ◽  
...  

The study aimed to evaluate the possible modulation of Nrf2, NF-ĸB and STAT3 signaling pathways in the colorectal cancer (CRC) cells line DLD-1 and HCT116 by secondary metabolites of lichens. An attempt was made to indicate the most promising targets in these signaling pathways. Attention was also paid to the effects of the compounds tested on CRC cells using anakoinosis—that is, simultaneous analysis of several signaling pathways. The effects of the tested natural compounds on the activity of selected transcriptional factors related to CRC were analyzed by Western blot and RT-PCR assays. The highest activity against CRC cells was shown by physodic and salazinic acids from the studied secondary metabolites of lichens. As a result, an increase in the activation of transcription factor Nrf2 and the expression of its selected target genes was observed. Physodic and salazinic acids induced the opposite effect in relation to the NF-κB and STAT3 pathways. These results confirmed our earlier observations that lichen-derived compounds have the ability to modulate signaling pathway networks. While caperatic acid affected Wnt/β-catenin to the most extent, salazinic acid was the most potent modulator of Nrf2, NF-κB and STAT3 pathways. Physodic acid seemed to affect all the investigated pathways.


2020 ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Hua Cao

Abstract Background: Heart failure is one of leading cause of death worldwide. However, the transcriptional profiling of heart failure is unclear. Moreover, the signaling pathways and transcription factors involving the heart failure development also are largely unknown. Using published Gene Expression Omnibus (GEO) datasets, in the present study, we aim to comprehensively analyze the differentially expressed genes in failing heart tissues, and identified the critical signaling pathways and transcription factors involving heart failure development. Methods: The transcriptional profiling of heart failure was identified from previously published gene expression datasets deposited in GSE5406, GSE16499 and GSE68316. The enriched signaling pathways and transcription factors were analyzed using DAVID website and gene set enrichment analysis (GSEA) assay. The transcriptional networks were created by Cytoscape. Results: Compared with the normal heart tissues, 90 genes were particularly differentially expressed in failing heart tissues, and those genes were associated with multiple metabolism signaling pathways and insulin signaling pathway. Metabolism and insulin signaling pathway were both inactivated in failing heart tissues. Transcription factors MYC and C/EBPβ were both negatively associated with the expression profiling of failing heart tissues in GSEA assay. Moreover, compared with normal heart tissues, MYC and C/EBPβ were down regulated in failing heart tissues. Furthermore, MYC and C/EBPβ mediated downstream target genes were also decreased in failing heart tissues. MYC and C/EBPβ were positively correlated with each other. At last, we constructed MYC and C/EBPβ mediated regulatory networks in failing heart tissues, and identified the MYC and C/EBPβ target genes which had been reported involving the heart failure developmental progress. Conclusions: Our results suggested that metabolism pathways and insulin signaling pathway, transcription factors MYC and C/EBPβ played critical roles in heart failure developmental progress.


2017 ◽  
Vol 53 (6) ◽  
pp. 725-739 ◽  
Author(s):  
Guang-Li Sun ◽  
Zheng Li ◽  
Wei-Zhi Wang ◽  
Zheng Chen ◽  
Lei Zhang ◽  
...  

2020 ◽  
Author(s):  
Yu Gong ◽  
Xiaoyang Qi ◽  
Jinjin Fu ◽  
Jun Qian ◽  
Yuwen Jiao ◽  
...  

Abstract Background: Increasing evidence implicates circular RNAs (circRNAs) have been involved in human cancer progression. However, the mechanism remains unclear. In this study, we identified novel circRNAs related to gastric cancer and constructed a circRNA-miRNA-mRNA network.Methods: Microarray dataset GSE83521 and GSE93541 were obtained from Gene Expression Omnibus (GEO). Then, we used computational biology to select differentially co-expressed circRNAs in GC tissue and plasma and detected the expression of selected circRNAs in gastric cell lines by quantitative real‑time polymerase chain reaction (qRT‑PCR). We also chose the candidate miRNAs and their target genes for circRNAs through online tools. Combining the predictions of miRNAs and target mRNAs, a competing endogenous RNA regulatory network was established. Functional and pathway enrichment analyses were performed, and interactions between proteins were predicted by using String and Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the possible functions of these differentially expressed circRNAs.Results: The regulatory network constructed using the microarray datasets (GSE83521 and GSE93541) contained three differentially co-expressed circRNAs (DECs). A circRNA-miRNA-mRNA network was constructed based on 3 circRNAs, 43 miRNAs and 119 mRNAs. GO and KEGG analysis showed that regulation of apoptotic signaling pathway and PI3K−Akt signaling pathway were highest degrees of enrichment respectively. We established a protein-protein interaction (PPI) network consisting of 165 nodes and 170 edges and identified hub genes by MCODE plugin in Cytoscape. Furthermore, a core circRNA-miRNA-mRNA network was constructed base on hub genes. Hsa_circ_0001013 was finally determined to play an important role in the pathogenesis of GC according to the core circRNA-miRNA-mRNA network.Conclusions: We propose a new circRNA-miRNA-mRNA network associated with the pathogenesis of GC. The network may become a new molecular biomarker and be used to develop potential therapeutic strategies for gastric cancer.


2020 ◽  
Vol 29 (6) ◽  
pp. 1295-1312
Author(s):  
Nazila Bostanshirin ◽  
Ahmad Bereimipour ◽  
Mohammad ali Pahlevan Neshan ◽  
Mina Aghasafi ◽  
Romina Mehtararaghinia ◽  
...  

2020 ◽  
Author(s):  
Yuan Wang ◽  
Chen Wang ◽  
Yu-Ting Mo ◽  
Wen Yi Tan ◽  
Xi-Yong Yu

Abstract Background According to the Cancer Genome Atlas, gastric cancers involve 30% BRD9 changes. Studying the signaling net controlled by BRD9 is important and provides useful information for the treatment of patients with gastric cancer and BRD9 alteration. Objective We performed this study to find the signaling pathways controlled by BRD9 in gastric cancer cells. Methods MGC-803 and AGS cells were selected as BRD9 overexpression and normal expression models, respectively, and added with BRD9 inhibitors BI9564 and BI7273, respectively. RNA-seq and limma R language were used to obtain differentially expressed genes (DEGs), and heatmap R language was employed for cluster analysis. Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to identify the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments, and STRING database was utilized to construct the protein–protein interaction (PPI) networks. Analysis was performed through Cytoscape software to determine the possible signaling pathway and target genes. Results Group MGC-803: 1204 and 1338 DEGs were found in MGC-803 cells added with BI9564 and BI7273, respectively, and 425 DEGs were found in the intersection of these two sets. AGS group: 974 and 1006 DEGs were found in AGS cells added with BI9564 and BI7273, respectively, and 382 DEGs were found in the intersection of these two sets. The DEG number in the intersection of groups MGC-803 and AGS was only 12, and only 3 of which showed the same regulation direction. Hence, these two types of gastric cancers are greatly altered in the signaling network. GO enrichment and KEGG signaling pathway analyses showed that in group MGC-803, BRD9 mainly controls cell adhesion molecule (CAM) pathway, and genes SPP1 and GNAO1 may play important an important role in the BRD9 controlling network. In group AGS, BRD9 mainly controls protein digestion and absorption pathway, and genes AR and GNGT2 have an important function in the BRD9 controlling network. Conclusion Comprehensive bioinformatics analyses were conducted to screen the DEGs and signaling pathways controlled by BRD9 in different gastric cancer cells. The findings provide a theoretical basis in curing patients with clinical gastric cancer.


2019 ◽  
Vol 156 (6) ◽  
pp. S-374
Author(s):  
Siyuan Chen ◽  
Hanxing Wan ◽  
Jingjing Liu ◽  
Nannan Gao ◽  
Hui Dong

2021 ◽  
Author(s):  
Hui Liu ◽  
Mangaladoss Fredimoses ◽  
Peijia Niu ◽  
Tingting Liu ◽  
Yan Qiao ◽  
...  

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