Additional effects of simultaneous treatment with C14-Cblin and celastrol on the clinorotation-induced rat L6 myotube atrophy

Kitahata, Kanako; Uchida, Takayuki; Taniguchi, Runa; Kato, Ayano; Sugiura, Kosuke; Sakakibara, Iori; Oarada, Motoko; Fukawa, Tomoya; Junsoo, Park; Choi, Inho; Nikawa, Takeshi

doi:10.2152/jmi.69.127

Cited by 1 publication

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“…The proliferation of tumor cells results in the secretion of a large number of vesicles, including exosomes, which may play a broad regulatory role in the development of cancer cachexia ( Rao et al, 2020 ). Celastrol has been reported in the past literature to have anticancer effects on colon cancer ( Moreira et al, 2022 ), inhibit colorectal cancer by inducing apoptosis in colorectal cancer cells ( Zhang H. et al, 2022 ), have significant inhibitory effects on colorectal cancer ( Wang S. et al, 2019 ), have good therapeutic effects on muscle atrophy ( Kitahata et al, 2022 ), resist muscle atrophy ( Gwag et al, 2013 ), and induce muscle fiber preservation ( Gwag et al, 2015 ). In our present study, we used bioinformatics to analyze the potential miRNA‒mRNA regulatory network of colorectal cancer via exosomes to regulate muscle atrophy through network pharmacology and the AI AlphaFold2 in an attempt to elucidate the possible regulatory mechanisms of celastrol via the miRNA‒mRNA regulatory network on colorectal cancerous muscle atrophy.…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics, network pharmacology, and artificial intelligence to predict the mechanism of celastrol against muscle atrophy caused by colorectal cancer

Zhang

2022

Front. Genet.

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Muscle atrophy due to colorectal cancer severely reduces the quality of life and survival time of patients. However, the underlying causative mechanisms and therapeutic agents are not well understood. The aim of this study was to screen and identify the microRNA (miRNA)–mRNA regulatory network and therapeutic targets of celastrol in colorectal cancer causing muscle atrophy via blood exosomes. Datasets were downloaded from the Gene Expression Omnibus online database. Differential expression analysis was first performed using the blood exosome dataset GSE39833 from colorectal cancer and normal humans to identify differentially expressed (DE) miRNAs, and then, transcriptional enrichment analysis was performed to identify important enriched genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by FunRich software. Using the muscle atrophy sample GSE34111, the DE mRNAs in the muscle atrophy sample were analyzed, a regulatory network map was established based on miRNA‒mRNA regulatory mechanisms, further GO and KEGG enrichment analyses were performed for the DE genes in muscle atrophy via Cytoscape’s ClueGO plug-in, and the network pharmacology pharmacophore analysis method was used to analyze the celastrol therapeutic targets, taking intersections to find the therapeutic targets of celastrol, using the artificial intelligence AlphaFold2 to predict the protein structures of the key targets, and finally using molecular docking to verify whether celastrol and the target proteins can be successfully docked. A total of 82 DE miRNAs were obtained, and the top 10 enriched target genes were identified. The enrichment of the 82 miRNAs showed a close correlation with muscle atrophy, and 332 DE mRNAs were found by differential expression analysis in muscle atrophy samples, among which 44 mRNA genes were involved in miRNA‒mRNA networks. The DE genes in muscle atrophy were enriched for 30 signaling pathways, and 228 target genes were annotated after pharmacophore target analysis. The NR1D2 gene, the target of treatment, was found by taking intersections, the protein structure of this target was predicted by AlphaFold2, and the structure was successfully docked and validated using molecular docking. In our present study, colorectal cancer likely enters the muscle from blood exosomes and regulates skeletal muscle atrophy through miRNA‒mRNA regulatory network mechanisms, and celastrol treats muscle through NR1D2 in the miRNA‒mRNA regulatory network.

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Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics, network pharmacology, and artificial intelligence to predict the mechanism of celastrol against muscle atrophy caused by colorectal cancer

Zhang

2022

Front. Genet.

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Additional effects of simultaneous treatment with C14-Cblin and celastrol on the clinorotation-induced rat L6 myotube atrophy

Cited by 1 publication

References 16 publications

Integrated bioinformatics, network pharmacology, and artificial intelligence to predict the mechanism of celastrol against muscle atrophy caused by colorectal cancer

Integrated bioinformatics, network pharmacology, and artificial intelligence to predict the mechanism of celastrol against muscle atrophy caused by colorectal cancer

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