Identification of Novel Genes and Associated Drugs in Advanced Clear Cell Renal Cell Carcinoma by Bioinformatic Methods

Lu, Meiqi; Lin, Xiao Jun; Xu, Bo; Gao, Qing

doi:10.1620/tjem.2022.j059

Cited by 4 publications

(3 citation statements)

References 61 publications

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“…Interestingly, our study revealed TOP2A as the key hub gene in the PBMCs of individuals who received the second dose of COVID-19 mRNA vaccine, indicating a potential similarity between COVID-19 infection (live virus) and vaccination (spike protein of the virus) to some extent. Previous research on TOP2A primarily focused on kidney cancer, where its upregulation was associated with prognosis and considered a potential target for mRNA vaccine development [38][39][40][41][42][43][44][45][46]. TOP2A was upregulated in kidney cancer, could predict the prognosis, and might be a tumor target to guide mRNA vaccine development [40,47].…”

Section: Discussionmentioning

confidence: 99%

Molecular Pathogenic Mechanisms of IgA Nephropathy Secondary to COVID-19 mRNA Vaccination

Wang,

Mao,

Zhang

et al. 2024

Kidney Blood Press Res

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Introduction: Accumulating evidence has disclosed that IgA nephropathy (IgAN) could present shortly after the second dose of COVID-19 mRNA vaccine. However, the undying mechanism remains unclear and we aimed to investigate the potential molecular mechanisms. Methods: We downloaded gene expression datasets of COVID-19 mRNA vaccination (GSE201535) and IgAN (GSE104948). Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to identify co-expression modules related to the second dose of COVID-19 mRNA vaccination and IgAN. Differentially expressed genes (DEGs) were screened, and a transcription factor (TF)-miRNA regulatory network and protein-drug interaction were constructed for the shared genes. Results: WGCNA identified one module associated with the second dose of COVID-19 mRNA vaccine and four modules associated with IgAN. Gene Ontology (GO) analyses revealed enrichment of cell cycle-related processes for the COVID-19 mRNA vaccine hub genes and immune effector processes for the IgAN hub genes. We identified 74 DEGs for the second dose of COVID-19 mRNA vaccine and 574 DEGs for IgAN. Intersection analysis with COVID-19 vaccine-related genes led to the identification of two shared genes, TOP2A and CEP55. The TF-miRNA network analysis showed that hsa-miR-144 and ATF1 might regulate the shared hub genes. Conclusions: This study provides insights into the common pathogenesis of COVID-19 mRNA vaccination and IgAN. The identified pivotal genes may offer new directions for further mechanistic studies of IgAN secondary to COVID-19 mRNA vaccination.

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Section: Discussionmentioning

confidence: 99%

Molecular Pathogenic Mechanisms of IgA Nephropathy Secondary to COVID-19 mRNA Vaccination

Wang,

Mao,

Zhang

et al. 2024

Kidney Blood Press Res

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“…(vii) Amonafide, a naphthalimide, was initially tested to treat acute myeloid leukemia and breast cancer. By intercalating DNA and blocking the binding of topoisomerases, amonafide promotes apoptotic cell death [96] and was effective against HepG2 and Huh7 cells [97]. The synthetic aminoacridine derivative (viii) amsacrine has a mechanism of action similar to amonafide and showed potential effects in treating malignant lymphoma and acute myeloid leukemia [98].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Profiling and Therapeutic Insights into Differentially Expressed Genes in Hepatocellular Carcinoma

Caputo,

de Souza,

Basso

et al. 2023

Cancers

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Background: Drug repurposing is a strategy that complements the conventional approach of developing new drugs. Hepatocellular carcinoma (HCC) is a highly prevalent type of liver cancer, necessitating an in-depth understanding of the underlying molecular alterations for improved treatment. Methods: We searched for a vast array of microarray experiments in addition to RNA-seq data. Through rigorous filtering processes, we have identified highly representative differentially expressed genes (DEGs) between tumor and non-tumor liver tissues and identified a distinct class of possible new candidate drugs. Results: Functional enrichment analysis revealed distinct biological processes associated with metal ions, including zinc, cadmium, and copper, potentially implicating chronic metal ion exposure in tumorigenesis. Conversely, up-regulated genes are associated with mitotic events and kinase activities, aligning with the relevance of kinases in HCC. To unravel the regulatory networks governing these DEGs, we employed topological analysis methods, identifying 25 hub genes and their regulatory transcription factors. In the pursuit of potential therapeutic options, we explored drug repurposing strategies based on computational approaches, analyzing their potential to reverse the expression patterns of key genes, including AURKA, CCNB1, CDK1, RRM2, and TOP2A. Potential therapeutic chemicals are alvocidib, AT-7519, kenpaullone, PHA-793887, JNJ-7706621, danusertibe, doxorubicin and analogues, mitoxantrone, podofilox, teniposide, and amonafide. Conclusion: This multi-omic study offers a comprehensive view of DEGs in HCC, shedding light on potential therapeutic targets and drug repurposing opportunities.

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“…2,10 Network pharmacology (NP) and molecular docking (MD) offer a comprehensive grasp of network theory and system biology, which contributes to the account for the mechanism of medications. 15 Previous studies using NP and MD have revealed the possible targets and mechanisms of HCQ treatment in autoimmune diseases. 16,17 The current study retrieved possible targets of LN, IgAN, and HCQ by data mining.…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology and molecular docking to elucidate the common mechanism of hydroxychloroquine treatment in lupus nephritis and IgA nephropathy

Chen,

Lu,

Lin

et al. 2024

Lupus

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Objective Hydroxychloroquine (HCQ), characterized by a broad effect on immune regulation, has been widely used in the treatment of autoimmune glomerulonephritis such as lupus nephritis (LN) and immunoglobulin A nephropathy (IgAN). The current research investigates whether HCQ plays a role in the treatment of LN and IgAN through common mechanisms since the pathogenesis of both LN and IgAN is closely related to immune complex deposition, complement activation, and ultimately inflammation. Methods Seventy-two common targets were obtained related to the common mechanism of HCQ treatment of LN and IgAN. Targets associated with LN and IgAN were collected based on DisGeNET, GeneCards, and OMIM databases. Possible HCQ targets were obtained from the PubChem database and PharmMapper databases. The overlapping targets of HCQ ingredients, IgAN, and LN were discovered via the Venn 2.1.0 online platform. Through the DAVID database, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. Cytoscape (v3.9.1) was used to build a protein–protein interaction (PPI) network. Molecular docking was performed by using AutoDockTools 1.5.6 software and PyMol software to match the binding activity between HCQ and the 10 core targets. Results The results showed that core targets (including MMP 2, PPARG, IL-2, MAPK14, MMP 9, and SRC), three signaling pathways (including the PI3K-Akt, AGE-RAGE, and MAPK), and cell differentiation (including Th1, Th2, and Th17) might be related to the body’s immunity and inflammation. These results suggested that HCQ might act on targets and pathways involved in inflammation and immune regulation to exert a common effect on the treatment of LN and IgAN. Conclusions The current study provided new evidence for the protective mechanism and clinical utility of HCQ against LN and IgAN.

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Identification of Novel Genes and Associated Drugs in Advanced Clear Cell Renal Cell Carcinoma by Bioinformatic Methods

Abstract: Identification of novel genes and associated drugs in advanced clear cell renal cell carcinoma by bioinformatic methods

Cited by 4 publications

References 61 publications

Molecular Pathogenic Mechanisms of IgA Nephropathy Secondary to COVID-19 mRNA Vaccination

Molecular Pathogenic Mechanisms of IgA Nephropathy Secondary to COVID-19 mRNA Vaccination

Comprehensive Profiling and Therapeutic Insights into Differentially Expressed Genes in Hepatocellular Carcinoma

Network pharmacology and molecular docking to elucidate the common mechanism of hydroxychloroquine treatment in lupus nephritis and IgA nephropathy

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