title: E2F, HSF2, and miR-26 in thyroid carcinoma: bioinformatic analysis of RNA-sequencing data.
abstract: In this study, we examined the molecular mechanism of thyroid carcinoma (THCA) using bioinformatics. RNA-sequencing data of THCA (N = 498) and normal thyroid tissue (N = 59) were downloaded from The Cancer Genome Atlas. Next, gene expression levels were calculated using the TCC package and differentially expressed genes (DEGs) were identified using the edgeR package. A co-expression network was constructed using the EBcoexpress package and visualized by Cytoscape, and functional and pathway enrichment of DEGs in the co-expression network was analyzed with DAVID and KOBAS 2.0. Moreover, modules in the co-expression network were identified and annotated using MCODE and BiNGO plugins. Small-molecule drugs were analyzed using the cMAP database, and miRNAs and transcription factors regulating DEGs were identified by WebGestalt. A total of 254 up-regulated and 59 down-regulated DEGs were identified between THCA samples and controls. DEGs enriched in biological process terms were related to cell adhesion, death, and growth and negatively correlated with various small-molecule drugs. The co-expression network of the DEGs consisted of hub genes (ITGA3, TIMP1, KRT19, and SERPINA1) and one module (JUN, FOSB, and EGR1). Furthermore, 5 miRNAs and 5 transcription factors were identified, including E2F, HSF2, and miR-26. miR-26 may participate in THCA by targeting CITED1 and PLA2R1; E2F may participate in THCA by regulating ITGA3, TIMP1, KRT19, EGR1, and JUN; HSF2 may be involved in THCA development by regulating SERPINA1 and FOSB; and small-molecule drugs may have anti-THCA effects. Our results provide novel directions for mechanistic studies and drug design of THCA.
authors.affiliation: Department of Endocrinology, Changhai Hospital, Shanghai, China.
authors.forename: J C
authors.initials: JC
authors.lastname: Lu
authors.affiliation: Department of Endocrinology, Changhai Hospital, Shanghai, China.
authors.forename: Y P
authors.initials: YP
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D019295:Computational Biology; D050684:E2F Transcription Factors; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006360:Heat-Shock Proteins; D006801:Humans; D035683:MicroRNAs; D017423:Sequence Analysis, RNA; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000235:genetics*; D014157:Transcription Factors; D059467:Transcriptome
chemical_list: D000970:Antineoplastic Agents; D050684:E2F Transcription Factors; D006360:Heat-Shock Proteins; D035683:MicroRNAs; D014157:Transcription Factors; C528163:MIRN26 microRNA, human; C070389:HSF2 protein, human