Knockdown of MMP‑1 inhibits the progression of colorectal cancer by suppressing the PI3K/Akt/c‑myc signaling pathway and EMT

Wang, Kai; Zheng, Jianbao; Yu, Ji Hee; Wu, Yunhua; Guo, Jing; Xu, Zhengshui; Sun, Xuejun

doi:10.3892/or.2020.7490

Cited by 47 publications

(57 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that baicalein could inhibit MMP-1 expression [ 27 ], and our study verified that bicycling and MMP-1 exhibit high binding energy through molecular docking. However, the downregulation of MMP‑1 expression inhibited the progression of colorectal cancer [ 28 ], it could thus be speculated that baicalein could slow down the progression of colorectal cancer by inhibiting MMP-1 expression. Kaempferol exhibits strong cytotoxic, anti-oxidant, anti-proliferative, and anti-apoptotic effects against HCT-116, HCT-15, SW480, and other CRC cells [ 29 ], and could also be used alone or combined with 5-FU to overcome CRC drug resistance [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Besides, CA 2 overexpression can improve the CRC cells’ sensitivity to chemotherapy drugs, which may be a potential biomarker for early CRC diagnosis [ 38 ]. Research shows that the expression of MMP-1 in colorectal cancer tissues is higher than that in normal colon tissues, and MMP-1 may influence the occurrence and development of colorectal cancer through EMT and Akt signaling pathways [ 28 ]. In conclusion, the targets of the XCHT active ingredients interact with the disease targets of CRC, giving full play to the unique advantages of multi-compounds and multi-targets of traditional Chinese medicine to prevent and treat CRC.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Network pharmacology and molecular docking study on the mechanism of colorectal cancer treatment using Xiao-Chai-Hu-Tang

et al. 2021

View full text Add to dashboard Cite

Background and objective We aimed to predict the targets and signal pathways of Xiao-Chai-Hu-Tang (XCHT) in the treatment of colorectal cancer (CRC) based on network pharmacology, just as well as to further analyze its anti-CRC material basis and mechanism of action. Methods We adopted Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID) databases to screen the active ingredients and potential targets of XCHT. CRC-related targets were retrieved by analyzing published microarray data (accession number GSE110224) from the Gene Expression Omnibus (GEO) database. The common targets were used to construct the “herb-active ingredient-target” network using the Cytoscape 3.8.0 software. Next, we constructed and analyzed protein-to-protein interaction (PPI) using BisoGenet and CytoNCA plug-in in Cytoscape. We then performed Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses of target genes using the R package of clusterProfiler. Furthermore, we used the AutoDock Tools software to conduct molecular docking studies on the active ingredients and key targets to verify the network pharmacological analysis results. Results We identified a total of 71 active XCHT ingredients and 20 potential anti-CRC targets. The network analysis revealed quercetin, stigmasterol, kaempferol, baicalein, and acacetin as potential key compounds, and PTGS2, NR3C2, CA2, and MMP1 as potential key targets. The active ingredients of XCHT interacted with most CRC disease targets. We showed that XCHT’s therapeutic effect was attributed to its synergistic action (multi-compound, multi-target, and multi-pathway). Our GO enrichment analysis showed 46 GO entries, including 20 biological processes, 6 cellular components, and 20 molecular functions. We identified 11 KEGG signaling pathways, including the IL-17, TNF, Toll-like receptor, and NF-kappa B signaling pathways. Our results showed that XCHT could play a role in CRC treatment by regulating different signaling pathways. The molecular docking experiment confirmed the correlation between five core compounds (quercetin, stigmasterol, kaempferol, baicalein, and acacetin) just as well as PTGS2, NR3C2, CA2, and MMP1. Conclusion In this study, we described the potential active ingredients, possible targets, and key biological pathways responsible for the efficacy of XCHT in CRC treatment, providing a theoretical basis for further research.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Network pharmacology and molecular docking study on the mechanism of colorectal cancer treatment using Xiao-Chai-Hu-Tang

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Matrix metalloproteinase-1 (MMP-1), also known as collagenase-1, has been demonstrated to mediate the pathological progression of diverse cancers [ 72 , 73 , 74 ]. Wang et al demonstrated that MMP-1 knockdown suppressed the progression of CRC by inhibiting the PI3K/Akt/c-myc signaling pathway and EMT [ 75 ]. All these results indicate that ECM-related EMT and IL-17 signaling pathways are strongly associated with the poor prognosis of right-sided colon cancers.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Proteomic Analysis of Colon Cancer Tissue Revealed the Reason for the Worse Prognosis of Right-Sided Colon Cancer and Mucinous Colon Cancer at the Protein Level

et al. 2021

View full text Add to dashboard Cite

To clarify the molecular mechanisms underlying the poor prognosis of right-sided and mucinous colon cancer at the proteomic level. A tandem mass tag-proteomics approach was used to identify differentially expressed proteins (DEPs) in colon carcinoma tissues from different locations and with different histological types to reveal the underlying mechanisms of these differences at the protein level. In additional, the DEPs were analyzed using bioinformatics methods. The proteomics profiles among colon cancers with different tumor locations and histological types were dramatically distinguished. In terms of tumor locations, the right-sided carcinoma specific DEPs may promote the tumor progression via activating inflammation, metastasis associated pathways. When referring to histological types, the mucinous colon cancers perhaps increased the invasion and metastasis through distinct mechanisms in different tumor locations. For mucinous cancer located in right-sided colon, the mucinous specific DEPs were mainly associated with ECM-related remodeling and the IL-17 signal pathway. For mucinous cancer located in left-sided colon, the mucinous specific DEPs showed a strong relationship with ACE2/Ang-(1–7)/MasR axis. The proteomics profiles of colon cancers showed distinct differences related to locations and histological types. These results suggested a distinct mechanism underlying the diverse subtypes of colon cancers.

show abstract

“…An increase in the CXCL8 level in the tumor microenvironment can promote the development of bladder cancer, and promote the angiogenesis and proliferation of tumor cells [18]. MMP1 is a mesenchymal collagen in the extracellular matrix, which involved in tumor behavior, and can promote the occurrence and metastasis of colorectal cancer through endothelial-mesenchymal transition and the protein kinase B signaling pathway [19]. ALB has an antioxidant effect in the blood vessels of people suffering from benign paroxysmal positional vertigo (BPPV), and a decrease in the serum level of ALB is related to BPPV pathogenesis [20].…”

Section: Discussionmentioning

confidence: 99%

Discovery of potential drugs to treat aggressive pituitary adenomas through text mining

Cai¹,

Sun²,

Shao³

et al. 2021

Preprint

View full text Add to dashboard Cite

Background Aggressive growth hormone-secreting pituitary adenomas (GHSPAs) account for 20–45% of GHSPAs. Although they are benign, treatment of GHSPAs is usually unsatisfactory.We wished to identify existing gene–drug interactions and expand the potential indications for new drugs to treat GHSPAs. Methods We used text mining with the keywords “growth hormone” and “visual disturbance” to obtain a common set of genes. These genes were analyzed using Genome Ontology and Kyoto Encyclopedia of Genes and Genomes databases, as well as protein–protein interaction networks. Finally, important genes clustered in PPI networks were selected for analyses of gene–drug interactions to identify potential drugs. Results Through text mining, we obtained 2848 genes related to growth hormone and 220 genes related to visual disturbance, and 157 genes were common to both. Common genes were clustered in significant gene modules. Finally, 12 of the 17 genes were targeted against 46 existing drugs: APOE, TRH, MMP2, ACE, CXCL8, MMP1, ALB, VEGFA, EDN1, TNF, PTH, and VWF. Conclusion Drug–gene interactions increase our understanding of the pathogenesis of invasive GHSPAs, and could be used in their prevention and treatment.

show abstract

Knockdown of MMP‑1 inhibits the progression of colorectal cancer by suppressing the PI3K/Akt/c‑myc signaling pathway and EMT

Cited by 47 publications

References 43 publications

Network pharmacology and molecular docking study on the mechanism of colorectal cancer treatment using Xiao-Chai-Hu-Tang

Network pharmacology and molecular docking study on the mechanism of colorectal cancer treatment using Xiao-Chai-Hu-Tang

Comprehensive Proteomic Analysis of Colon Cancer Tissue Revealed the Reason for the Worse Prognosis of Right-Sided Colon Cancer and Mucinous Colon Cancer at the Protein Level

Discovery of potential drugs to treat aggressive pituitary adenomas through text mining

Contact Info

Product

Resources

About