Protein-protein Interaction Network Analyses for Elucidating the Roles of LOXL2-delta72 in Esophageal Squamous Cell Carcinoma

Abstract

Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase (LOX) family, is a copper-dependent enzyme thatcatalyzes oxidative deamination of lysine residues on protein substrates. LOXL2 was found to be overexpressedin esophageal squamous cell carcinoma (ESCC) in our previous research. We later identified a LOXL2 splicingvariant LOXL2-delta72 and we overexpressed LOXL2-delta72 and its wild type counterpart in ESCC cellsfollowing microarray analyses. First, the differentially expressed genes (DEGs) of LOXL2 and LOXL2-delta72compared to empty plasmid were applied to generate protein-protein interaction (PPI) sub-networks. Comparisonof 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 PPIsub-network which was annotated by Gene Ontology. The functional annotation map indicated the third PPIsub-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” relatedterms, such as “innate immune response”, “regulation of defense response” and “Toll signaling pathway”. Theseresults provide important clues for experimental identification of the specific biological roles and molecularmechanisms of LOXL2-delta72. This study also provided a work flow to test the different roles of a splicingvariant with high-throughput data.