National Engineering Research Center for Miniaturized Detection Systems, Northwest University, Xi'an, P. R. China.
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Mol Omics. 2019 Apr 1;15(2):117-129. doi: 10.1039/c8mo00234g. Epub 2019 Feb 5.
Protein isoforms are structurally similar proteins produced by alternative splicing of a single gene or genes from the same family. Isoforms of a protein can perform the same, similar, or even opposite biological functions. A previous study identified principal isoforms of proteins based on the extent of interactions per isoform in a functional relationship network, focusing on data from normal tissues. Additionally, the expression levels of specific isoforms of various genes associated with tumorigenesis and prognosis are frequently altered in tumors compared with those in normal tissues. In this study, we aimed to identify higher degree isoforms (HDIs) of multi-isoform genes (MIGs) in cancer by applying a meta-analytical framework to calculate co-expression between each pair of isoforms in two large datasets of RNA-seq profiles from breast cancer, lung cancer, leukemia, and colon cancer cell lines. Then, we compared HDIs with isoforms identified by proteomic data and prognostic and predictive evidence in various cancers. In addition, we separately analyzed the associations between HDIs and non-HDIs (nHDIs) of the same genes according to transcript expression and drug responses in various cancer type cell lines. Collectively, these results indicated the complex properties of HDIs per gene identified by cancer type-based isoform-isoform co-expression networks and showed the potential of HDIs as novel therapeutic targets for cancer treatment.
蛋白质异构体是由同一基因或同一家族的基因通过选择性剪接产生的结构相似的蛋白质。蛋白质异构体可以执行相同、相似甚至相反的生物学功能。先前的研究基于功能关系网络中每个异构体的相互作用程度，确定了蛋白质的主要异构体，重点是来自正常组织的数据。此外，与正常组织相比，肿瘤中与肿瘤发生和预后相关的各种基因的特定异构体的表达水平经常发生改变。在这项研究中，我们旨在通过应用元分析框架来确定癌症中的多异构体基因 (MIG) 的高程度异构体 (HDI)，该框架用于计算来自乳腺癌、肺癌、白血病和结肠癌细胞系的两个大型 RNA-seq 图谱数据集的每对异构体之间的共表达。然后，我们将 HDIs 与蛋白质组学数据以及各种癌症中的预后和预测证据确定的异构体进行了比较。此外，我们还根据各种癌症类型细胞系中的转录表达和药物反应，分别分析了 HDIs 与同一基因的非 HDIs (nHDIs) 之间的关联。总之，这些结果表明了基于癌症类型的异构体-异构体共表达网络中每个基因的 HDIs 的复杂特性，并显示了 HDIs 作为癌症治疗新的治疗靶点的潜力。
