Network analyses elucidate the role of SMYD3 in esophageal squamous cell carcinoma

SMYD 3 is a member of the SET and myeloid‐Nervy‐DEAF‐1 (MYND) domain‐containing protein family of methyltransferases, which are known to play critical roles in carcinogenesis. Expression of SMYD 3 is elevated in various cancers, including esophageal squamous cell carcinoma (ESCC), and is correlated with the survival time of patients with ESCC . Here, we dissect gene expression data, from a previously described KYSE 150 ESCC cell line in which SMYD 3 had been knocked down, by integration with the protein–protein interaction ( PPI ) network, to find the new potential biological roles of SMYD 3 and subsequent target genes. By construction of a specific PPI network, differentially expressed genes ( DEG s), following SMYD 3 knockdown, were identified as interacting with thousands of neighboring proteins. Enrichment analyses from the DAVID Functional Annotation Chart found significant Gene Ontology ( GO ) terms associated with transcription activities, which were closely related to SMYD 3 function. For example, YAP 1 and GATA 3 might be a target gene for SMYD 3 to regulate transcription. Enrichment annotation of the total DEG PPI network by GO ‘Biological Process’ generated a connected functional map and found 532 significant terms, including known and potential biological roles of SMYD 3 protein, such as expression regulation, signal transduction, cell cycle, cell metastasis, and invasion. Subcellular localization analyses found that DEG s and their interacting proteins were distributed in multiple layers, which might reflect the intricate biological processes at the spatial level. Our analysis of the PPI network has provided important clues for future detection of the biological roles and mechanisms, as well as the target genes of SMYD 3.