title: Exploration of potential roles of a new LOXL2 splicing variant using network knowledge in esophageal squamous cell carcinoma.
abstract: LOXL2 (lysyl oxidase-like 2), an enzyme that catalyzes oxidative deamination of lysine residue, is upregulated in esophageal squamous cell carcinoma (ESCC). A LOXL2 splice variant LOXL2-e13 and its wild type were overexpressed in ESCC cells followed by microarray analyses. In this study, we explored the potential role and molecular mechanism of LOXL2-e13 based on known protein-protein interactions (PPIs), following microarray analysis of KYSE150 ESCC cells overexpressing a LOXL2 splice variant, denoted by LOXL2-e13, or its wild-type counterpart. The differentially expressed genes (DEGs) of LOXL2-WT and LOXL2-e13 were applied to generate individual PPI subnetworks in which hundreds of DEGs interacted with thousands of other proteins. These two DEG groups were annotated by Functional Annotation Chart analysis in the DAVID bioinformatics database and compared. These results found many specific annotations indicating the potential specific role or mechanism for LOXL2-e13. The DEGs of LOXL2-e13, comparing to its wild type, were prioritized by the Random Walk with Restart algorithm. Several tumor-related genes such as ERO1L, ITGA3, and MAPK8 were found closest to LOXL2-e13. These results provide helpful information for subsequent experimental identification of the specific biological roles and molecular mechanisms of LOXL2-e13. Our study also provides a work flow to identify potential roles of splice variants with large scale data.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Bing-Li
authors.initials: BL
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Lv
authors.affiliation: Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zou
authors.affiliation: Department of Pathology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, Guangdong 515041, China.
authors.forename: Ze-Peng
authors.initials: ZP
authors.lastname: Du
authors.affiliation: Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Jian-Yi
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Pi-Xian
authors.initials: PX
authors.lastname: Zhang
authors.affiliation: Institute of Oncologic Pathology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041, China.
authors.forename: En-Min
authors.initials: EM
authors.lastname: Li
mesh_terms: D000465:Algorithms; D017398:Alternative Splicing; D000594:Amino Acid Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps / Q000235:genetics
chemical_list: D007527:Isoenzymes; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human