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

Abstract

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 were analyzed 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, actin filament binding and actin cytoskeleton, which might be related to fascin function. Except GO categories, the differentially expressed genes were annotated by 45 functional categories from the Functional Annotation Chart of DAVID. Subpathway analysis showed thirty-nine pathways were disturbed by the differentially expressed genes, providing more detailed information than traditional pathway enrichment analysis. Two subpathways derivated from regulation of the actin cytoskeleton were shown. Promoter analysis results indicated distinguishing sequence patterns and transcription factors in response to the co-expression of downregulated or upregulated differentially expressed genes. MNB1A, c-ETS, GATA2 and Prrx2 potentially regulate the transcription of the downregulated gene set, while Arnt-Ahr, ZNF42, Ubx and TCF11-MafG might co-regulate the upregulated genes. Conclusions: This multiple bioinformatic analysis helps provide a comprehensive understanding of the roles of fascin after its knockdown in ESCC.

Tumor-suppressive effects of microRNA-181d-5p on non-small-cell lung cancer through the CDKN3-mediated Akt signaling pathway in vivo and in vitro

“…NSCLC accounts for~80% of all lung cancer cases, which further consists of three major subtypes: squamous cell carcinoma, adenocarcinoma, and large-cell carcinoma, which are differentiated on the basis of pathological characteristics (49,54). The three most commonly applied treatment methods for NSCLC include surgery, chemotherapy, and radiotherapy (13,48). However, because of a number of side effects, including chemotherapy-induced cell death, the above treatments have a low efficacy (17).…”

In silico docking of methyl isocyanate (MIC) and its hydrolytic product (1, 3-dimethylurea) shows significant interaction with DNA Methyltransferase 1 suggests cancer risk in Bhopal-Gas-Tragedy survivors

“…With the use of computational methods, numerous studies have discovered that several cancers are markedly triggered by epigenetic alterations (Mahdavi et al, 2012;Wu et al, 2013;Jiang et al, 2014;Song et al, 2014;Zhuo e t al., 2014;Wang and Yan, 2015). The present study was also an attempt to determine the in silico interaction of MIC and 1,3-dimethylurea with several domains of DNMT1.…”

Fascin and esophageal squamous cell carcinoma

“…After validating cDNA microarray data by real‐time reverse transcription polymerase chain reaction, western blot, and immunofluorescence analyses, we found that two genes, CYR61 (cysteine‐rich, angiogenic inducer 61) and CTGF (connective tissue growth factor), were downregulated through the transforming growth factor‐β signaling pathway, and were directly involved in the fascin‐mediated proliferation and invasiveness of ESCC cells . Furthermore, to comprehensively understand the mRNA profile of fascin knockdown in the ESCC cell line, EC109, and to illustrate the functional roles of fascin, we carried out multiple bioinformatics analyses for differentially expressed genes, including gene ontology enrichment and functional annotation analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, promoter sequence analysis, and protein‐protein interaction sub‐network analysis . Gene ontology term enrichment found that fascin was associated with cytoskeleton organization, including cell adhesion, F‐actin filament binding, and F‐actin cytoskeleton.…”

“…The promoter sequence analysis showed that transcription factors MNB1A, c‐ETS, GATA2 and Prrx2 potentially regulated the downregulated gene set, whereas Arnt‐Ahr, ZNF 41, Ubx and TCF11‐MafG potentially co‐regulated the upregulated gene set. The protein–protein interaction sub‐network analysis showed that differentially expressed genes interacted with other proteins directly or indirectly in multiple subcellular layers of the extracellular membrane–cytoskeleton/cytoplasm–nucleus …”