背景:骨骼肌萎缩在许多慢性疾病并发症中普遍存在。尽管具有重要的临床意义,目前没有治疗药物,因此,迫切需要发现新的生物标志物和分子机制。
方法:从正常和骨骼肌萎缩性小鼠收集转录组和蛋白质组测序数据。分析差异表达基因(DEG)和蛋白质(DEP)。应用PPI分析获得重叠基因和蛋白质,接下来进行GO和KEGG富集分析。进行转录组学和蛋白质组学的联合分析,以获得同时在GO和KEGG富集结果中发现的关键基因。随后,构建RT-qPCR和免疫荧光对筛选出的关键基因进行表达验证。
结果:通过结合转录组学,蛋白质组学分析和RT-qPCR结果,我们确定了14个关键基因(Cav1,Col3a1,Dnaja1,Postn,Ptges3,Cd44,Clec3b,Igfbp6,Lamc1,Alb,Itga6,Mmp2,Timp2和Cd9)在萎缩性小鼠中明显不同。单基因GSEA和免疫荧光提示Cd9可能是骨骼肌萎缩的生物标志物。
结论:我们的研究表明,Cd9是潜在的生物标志物,可能通过有氧呼吸过程干扰骨骼肌萎缩,氧化磷酸化,以及氨基酸和脂肪酸的代谢。
结论:本研究具有后续意义:首先,我们使用多组学方法研究了骨骼肌萎缩的生物标志物.在骨骼肌萎缩性小鼠中,共有14个基因显着不同。我们最终发现Cd9是骨骼肌萎缩的潜在生物标志物。我们的工作为肌肉萎缩的早期检测和干预提供了新的生物标志物和潜在的调节机制。
BACKGROUND: The skeletal muscle atrophy is prevalently occurred in numerous chronic disease complications. Despite its important clinical significance, there are currently no therapeutic drugs, so new biomarkers and molecular mechanisms need to be discovered urgently.
METHODS: Transcriptome and proteome sequencing data were collected from normal and skeletal muscle atrophic mice. The differentially expressed genes (DEGs) and proteins (DEPs) were analyzed. Applying PPI analysis to obtain overlapping genes and proteins, which were next subjected to GO and KEGG enrichment analysis. Combined analysis of transcriptomics and proteomics was performed to get key genes that were simultaneously found in GO and KEGG enrichment results. Subsequently, RT-qPCR and immunofluorescence were constructed to verify the expression of screened key genes.
RESULTS: By combination of transcriptomics, proteomics and RT-qPCR results, we identified 14 key genes (Cav1, Col3a1, Dnaja1, Postn, Ptges3, Cd44, Clec3b, Igfbp6, Lamc1, Alb, Itga6, Mmp2, Timp2 and Cd9) that were markedly different in atrophic mice. Single-gene GSEA and immunofluorescence suggested Cd9 was probably the biomarker for skeletal muscle atrophy.
CONCLUSIONS: Our study hinted that Cd9 was potential biomarker and may interfere with skeletal muscle atrophy through process of aerobic respiration, oxidative phosphorylation, and metabolism of amino acids and fatty acids.
CONCLUSIONS: The present study holds the subsequent significance: Frist, we investigated biomarkers for skeletal muscle atrophy using multi-omics approach. A total of 14 genes were markedly different in skeletal muscle atrophic mice. We finally found Cd9 is a potential biomarker for skeletal muscle atrophy. Our work presents novel biomarkers and potential regulatory mechanisms for the early detection and intervention of muscle atrophy.