Comparative transcriptome analyses revealed conserved biological and transcription factor target modules between the zebrafish and human tumors

Abstract

In an effort of validating the zebrafish model for studies of human tumors, our previous transcriptome analyses revealed striking molecular similarities between zebrafish and human liver neoplasia. However, as biological processes function at modular levels such as pathways and cascades, it is also important to capture conservation at the modular levels and in regulatory program(s) controlling these modules. In this study, we performed comparative transcriptome analyses with two modules, biological modules and transcription factor target modules, using gene set enrichment analysis against carcinogen-induced liver tumors in zebrafish with four tissue types of human tumors. We observed conservation of enriched modules that are associated to tumorigenesis such as cell cycle, metastasis, and hypoxia in these tumors. More importantly, we identified conserved regulatory programs linking these cancer-related modules with transcription factors and oncogenes such as Myc, E2F, STAT, and YY1. Taken together, our analyses revealed that carcinogen-induced liver tumors in zebrafish capture cancerous hallmarks observed in human tumors not only for cancer-related biological modules but also at transcriptional program, further implicating conserved tumorigenesis mechanism in both zebrafish and human. © Mary Ann Liebert, Inc.