Santos Lúcia, Nascimento Rui, Duarte Aires, Railean Violeta, Amaral Margarida D, Harrison Patrick T, Gama-Carvalho Margarida, Farinha Carlos M
BioISI - Instituto de Biossistemas e Ciências Integrativas, Faculdade de Ciências, Universidade de Lisboa, 1749-016, Lisbon, Portugal.
Department of Physiology, University College Cork, Cork, T12 K8AF, Ireland.
Cell Biosci. 2023 Feb 9;13(1):26. doi: 10.1186/s13578-023-00975-y.
The phenotypic heterogeneity observed in Cystic Fibrosis (CF) patients suggests the involvement of other genes, besides CFTR. Here, we combined transcriptome and proteome analysis to understand the global gene expression patterns associated with five prototypical CFTR mutations.
Evaluation of differentially expressed genes and proteins unveiled common and mutation-specific changes revealing functional signatures that are much more associated with the specific molecular defects associated with each mutation than to the CFTR loss-of-function phenotype. The combination of both datasets revealed that mutation-specific detected translated-transcripts (Dtt) have a high level of consistency.
This is the first combined transcriptomic and proteomic study focusing on prototypical CFTR mutations. Analysis of Dtt provides novel insight into the pathophysiology of CF, and the mechanisms through which each mutation class causes disease and will likely contribute to the identification of new therapeutic targets and/or biomarkers for CF.
在囊性纤维化（CF）患者中观察到的表型异质性表明，除CFTR外，其他基因也参与其中。在此，我们结合转录组和蛋白质组分析，以了解与五种典型CFTR突变相关的全局基因表达模式。
对差异表达基因和蛋白质的评估揭示了共同的和突变特异性的变化，这些变化揭示了功能特征，这些特征与每个突变相关的特定分子缺陷的关联程度远高于与CFTR功能丧失表型的关联程度。两个数据集的结合表明，突变特异性检测到的翻译转录本（Dtt）具有高度的一致性。
这是第一项聚焦于典型CFTR突变的转录组学和蛋白质组学联合研究。对Dtt的分析为CF的病理生理学以及每种突变类型导致疾病的机制提供了新的见解，并可能有助于识别CF的新治疗靶点和/或生物标志物。
