Wu Bing-Li, Zou Hai-Ying, Lv Guo-Qing, Du Ze-Peng, Wu Jian-Yi, Zhang Pi-Xian, Xu Li-Yan, Li En-Min
Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China E-mail :
Asian Pac J Cancer Prev. 2014;15(5):2345-51. doi: 10.7314/apjcp.2014.15.5.2345.
Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase (LOX) family, is a copper-dependent enzyme that catalyzes oxidative deamination of lysine residues on protein substrates. LOXL2 was found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous research. We later identified a LOXL2 splicing variant LOXL2-delta72 and we overexpressed LOXL2-delta72 and its wild type counterpart in ESCC cells following microarray analyses. First, the differentially expressed genes (DEGs) of LOXL2 and LOXL2-delta72 compared to empty plasmid were applied to generate protein-protein interaction (PPI) sub-networks. Comparison of these two sub-networks showed hundreds of different proteins. To reveal the potential specific roles of LOXL2- delta72 compared to its wild type, the DEGs of LOXL2-delta72 vs LOXL2 were also applied to construct a PPI sub-network which was annotated by Gene Ontology. The functional annotation map indicated the third PPI sub-network involved hundreds of GO terms, such as "cell cycle arrest", "G1/S transition of mitotic cell cycle", "interphase", "cell-matrix adhesion" and "cell-substrate adhesion", as well as significant "immunity" related terms, such as "innate immune response", "regulation of defense response" and "Toll signaling pathway". These results provide important clues for experimental identification of the specific biological roles and molecular mechanisms of LOXL2-delta72. This study also provided a work flow to test the different roles of a splicing variant with high-throughput data.
赖氨酰氧化酶样2（LOXL2）是赖氨酰氧化酶（LOX）家族的一员，是一种依赖铜的酶，可催化蛋白质底物上赖氨酸残基的氧化脱氨反应。在我们之前的研究中发现LOXL2在食管鳞状细胞癌（ESCC）中过表达。后来我们鉴定出一种LOXL2剪接变体LOXL2-δ72，并在微阵列分析后在ESCC细胞中过表达了LOXL2-δ72及其野生型对应物。首先，将与空质粒相比的LOXL2和LOXL2-δ72的差异表达基因（DEG）用于生成蛋白质-蛋白质相互作用（PPI）子网。对这两个子网的比较显示了数百种不同的蛋白质。为了揭示LOXL2-δ72与其野生型相比潜在的特定作用，还将LOXL2-δ72与LOXL2的DEG用于构建一个由基因本体注释的PPI子网。功能注释图表明第三个PPI子网涉及数百个GO术语，如“细胞周期停滞”、“有丝分裂细胞周期的G1/S转变”、“间期”、“细胞-基质粘附”和“细胞-底物粘附”，以及与“免疫”相关的重要术语，如“先天免疫反应”、“防御反应的调节”和“Toll信号通路”。这些结果为实验鉴定LOXL2-δ72的特定生物学作用和分子机制提供了重要线索。本研究还提供了一个工作流程，以通过高通量数据测试剪接变体的不同作用。
