Identification of potential targets of triptolide in regulating the tumor microenvironment of stomach adenocarcinoma patients using bioinformatics

Qiu, Hairong; Zhang, Xiaobo; Yu, Han; Gao, Rui; Shi, Jianglong; Shen, Tao

doi:10.1080/21655979.2021.1945522

Cited by 8 publications

(4 citation statements)

References 58 publications

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“…Solute carrier family 12 member 8 has been reported to be upregulated in bladder cancer and related to patient prognosis and tumor immune cell infiltration [ 83 ]. C-X-C chemokine receptor type 4 was identified as a therapeutic target of triptolide in the treatment of STAD patients by modulating the TME [ 84 ]. Domain-containing protein 1 has been reported upregulated in most cancers and played oncogenic roles in pan-cancer by comprehensive bioinformatic analysis [ 85 ].…”

Section: Discussionmentioning

confidence: 99%

A pan-cancer analysis of the prognostic and immunological role of β-actin (ACTB) in human cancers

Tang

Wang

et al. 2021

Bioengineered

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Beta-actin (ACTB), a highly conserved cytoskeleton structural protein, has been regarded as a common housekeep gene and used as a reference gene for years. However, accumulating evidence indicates that ACTB is abnormally expressed in multiple cancers and hence changes the cytoskeleton to affect the invasiveness and metastasis of tumors. This study aimed to investigate the function and clinical significance of ACTB in pan-cancer. The role of ACTB for prognosis and immune regulation across 33 tumors was explored based on the datasets of gene expression omnibus and the cancer genome atlas. Differential expression of ACTB was found between cancer and adjacent normal tissues, and significant associations was found between ACTB expression and prognosis of tumor patients. In most cancers, ACTB expression was associated with immune cells infiltration, immune checkpoints and other immune modulators. Relevance between ACTB and metastasis and invasion was identified in various types of cancers by CancerSEA. Moreover, focal adhesion and actin regulation-associated pathways were included in the functional mechanisms of ACTB. The expression of ACTB was verified by quantitative real-time polymerase chain reaction. Knockdown of ACTB inhibited head and neck squamous carcinoma cell migration and invasion by NF-κB and Wnt/β-catenin pathways. Our first pan-cancer study of ACTB offers insight into the prognostic and immunological roles of ACTB across different tumors, indicating ACTB may be a potential biomarker for poor prognosis and immune infiltration in cancers, and the role of ACTB as a reference gene in cancers was challenged.

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Section: Discussionmentioning

confidence: 99%

A pan-cancer analysis of the prognostic and immunological role of β-actin (ACTB) in human cancers

Tang

Wang

et al. 2021

Bioengineered

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“…We identified several cancer-related significantly enriched signaling pathways, mainly including ECM interaction and repair of genetic alteration, which are related to high NUDT10 expression in GC. The ECM is an important component of the tumor microenvironment and plays a key role in tumor progression and patient survival [ 25 ]. Zhou L, et al constructed a novel prognostic signature for GC based on large sequencing data and showed that ECM-receptor interaction is an important platform for the function of prognosis-related differentially expressed genes [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical correlations and prognostic value of Nudix hydroxylase 10 in patients with gastric cancer

et al. 2021

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Gastric cancer (GC) is one of the most common and lethal cancers worldwide. The Nudix hydroxylase (NUDT) genes have been reported to play notable roles in tumor progression. However, the role of NUDT10 in GC has not been reported. In this study, we investigated the expression of NUDT10 in GC and its association with clinicopathological characteristics. Quantitative real-time polymerase chain reaction and analyses of The Cancer Genome Atlas and Human Protein Atlas databases were performed to determine NUDT10 mRNA and protein expression. Receiver operating characteristic curve analysis was used to assess the diagnostic value of NUDT10 in patients with GC. We used Cox regression and the Kaplan–Meier method to assess the correlations between clinicopathological factors and survival outcomes of patients with GC. Gene set enrichment analysis (GSEA) was performed to identify the underlying signaling pathways. NUDT10 mRNA and protein expression was significantly lower in GC tissues compared to normal tissues. Interestingly, higher NUDT10 expression was correlated with advanced tumor stage, deeper local invasion, and worse survival outcomes. Patients with higher NUDT10 expression had a significantly worse prognosis than those with lower NUDT10 expression. Multivariate analysis showed that high NUDT10 expression was an independent predictor of survival outcome. Several pathways, including mismatch repair, nucleotide excision repair, extracellular matrix receptor interaction, and cancer signaling, were identified as enriched pathways in GC through GSEA. To our knowledge, this study is the first to characterize NUDT10 expression in GC. Our study demonstrates that NUDT10 is a promising independent biomarker for GC prognosis.

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“…The standardized proteins and ligands were imported into AutoDockTools (version 1.5.6) and converted into a PDBQT format. Using the AutoDock Vina software (version 1.1.2), we ran a program for molecular docking using docking parameters; the complex conformation with the minimum binding energy and highest binding affinity for each molecule was selected for further analysis [ 24 ]. Generally, the binding energy < 0 kcal/mol indicates that the ligand can bind to the receptor protein, while the binding energy ≤ −5.0 kcal/mol reveals that the ligand and the protein have a good binding ability [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

Pharmacological Mechanism of Ganlu Powder in the Treatment of NASH Based on Network Pharmacology and Molecular Docking

et al. 2022

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Nonalcoholic steatohepatitis (NASH), a progression of nonalcoholic fatty liver disease (NAFLD), is a clinical syndrome characterized by liver steatosis, inflammation, and hepatocellular damage. Ganlu powder (GLP) is a classic traditional Chinese medicine prescription that has shown favorable treatment effects on NASH. However, the underlying therapeutic mechanisms are still poorly understood. This study is aimed at exploring the potential mechanism of GLP in the treatment of NASH via network pharmacology and molecular docking. PubMed and CNKI databases were used to identify the components of GLP. Swiss and STITCH databases were employed to obtain corresponding drug targets. NASH targets were adopted from the Therapeutic Target Database (TTD), DisGeNET, DrugBank, GeneCards, and MalaCards databases. Cytoscape software was utilized to construct “drug-ingredient-target-disease” networks and the protein-protein interaction (PPI) network of GLP in NASH. AKT1 was identified as the key target. The GO functional enrichment analysis revealed that GLP might treat NASH by modulating the inflammatory response and regulating phosphatidylinositol 3-kinase signaling. The KEGG analysis showed that GLP might treat NASH by regulating the tumor necrosis factor (TNF) signal pathway by affecting the role of AKT1. According to the network pharmacology results, a virtual docking of active compounds with AKT1 was carried out, and the results indicated that the 7 components, berberine, epiberberine, jatrorrhizine, coptisine, palmatine, evodiamine, and rutecarpine, can bind stably with AKT1 and have higher binding energy than AKT1 inhibitors. The overall study findings suggest that GLP may treat NASH by regulating AKT1.

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Identification of potential targets of triptolide in regulating the tumor microenvironment of stomach adenocarcinoma patients using bioinformatics

Cited by 8 publications

References 58 publications

A pan-cancer analysis of the prognostic and immunological role of β-actin (ACTB) in human cancers

A pan-cancer analysis of the prognostic and immunological role of β-actin (ACTB) in human cancers

Clinical correlations and prognostic value of Nudix hydroxylase 10 in patients with gastric cancer

Pharmacological Mechanism of Ganlu Powder in the Treatment of NASH Based on Network Pharmacology and Molecular Docking

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