Comprehensive Bioinformation Analysis of the MRNA Profile of Fascin Knockdown in Esophageal Squamous Cell Carcinoma


Background: Fascin, an actin-bundling protein forming actin bundles including filopodia and stress fibers,is overexpressed in multiple human epithelial cancers including esophageal squamous cell carcinoma (ESCC).Previously we conducted a microarray experiment to analyze fascin knockdown by RNAi in ESCC.
Method:In this study, the differentially expressed genes from mRNA expression profilomg of fascin knockdown wereanalyzed by multiple bioinformatics methods for a comprehensive understanding of the role of fascin.
Results:Gene Ontology enrichment found terms associated with cytoskeleton organization, including cell adhesion, actinfilament binding and actin cytoskeleton, which might be related to fascin function. Except GO categories, thedifferentially expressed genes were annotated by 45 functional categories from the Functional Annotation Chartof DAVID. Subpathway analysis showed thirty-nine pathways were disturbed by the differentially expressedgenes, providing more detailed information than traditional pathway enrichment analysis. Two subpathwaysderivated from regulation of the actin cytoskeleton were shown. Promoter analysis results indicated distinguishingsequence patterns and transcription factors in response to the co-expression of downregulated or upregulateddifferentially expressed genes. MNB1A, c-ETS, GATA2 and Prrx2 potentially regulate the transcription of thedownregulated gene set, while Arnt-Ahr, ZNF42, Ubx and TCF11-MafG might co-regulate the upregulatedgenes.
Conclusions: This multiple bioinformatic analysis helps provide a comprehensive understanding of theroles of fascin after its knockdown in ESCC.