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- W4307510122 abstract "Abstract Objective. Duchenne muscular dystrophy (DMD) is a devastating X-linked neuromuscular disorder caused by various defects in the dystrophin gene and still no universal therapy. This study aims to identify the hub genes unrelated to excessive immune response but responsible for DMD progression and explore therapeutic siRNAs, thereby providing a novel treatment. Methods. Top ten hub gene for DMD were identified from GSE38417 dataset by using GEO2R and PPI network based on Cytoscape analysis. The hub genes unrelated to excessive immune response were identified by GeneCards, and their expression was further verified in mdx and C57 mice at 2 and 4 months (M) by (RT-q) PCR and western bloting. Therapeutic siRNAs were deemed as those that could normalized the expression of the validated hub genes in transfected C2C12 cell. Results. 855 up-regulated and 324 down-regulated DEGs were screened from GSE38417 dataset. Five of the top 10 hub genes were considered as the candidate genes unrelated to excessive immune response, and three of these candidates were consistently and significantly up-regulated in mdx mice at 2M and 4 M when compared with age-matched C57 mice, including Col1a2, Fbn1 and Fn1 . Furthermore, the three validated up-regulated candidate genes can be significantly down-regulated by three rational designed siRNA ( p <0.0001), respectively. Conclusion. COL1A2, FBN1, and FN1 may be novel biomarkers for DMD, and the siRNAs designed in our study were help to develop adjunctive therapy for Duchenne muscular dystrophy." @default.
- W4307510122 created "2022-11-02" @default.
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- W4307510122 date "2022-10-28" @default.
- W4307510122 modified "2023-09-28" @default.
- W4307510122 title "Identification of hub genes and therapeutic siRNAs to develop novel adjunctive therapy for Duchenne muscular dystrophy" @default.
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- W4307510122 doi "https://doi.org/10.21203/rs.3.rs-2184962/v1" @default.
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