关键词: BCL2 family RAS-PI3K-AKT-NF-κB pathway RNA sequencing apoptosis fibrous epulis

Mesh : Apoptosis / genetics Gene Expression Profiling Gene Expression Regulation Gene Ontology Gingiva / pathology Gingival Diseases / genetics pathology Humans Inhibitor of Apoptosis Proteins / genetics metabolism Molecular Sequence Annotation Multigene Family NF-kappa B / metabolism Phosphatidylinositol 3-Kinases / metabolism Proto-Oncogene Proteins c-akt / metabolism Proto-Oncogene Proteins c-bcl-2 / genetics metabolism Reproducibility of Results Signal Transduction / genetics Transcription, Genetic ras Proteins / metabolism

来  源:   DOI:10.1002/jcla.23102   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
BACKGROUND: Epulis has a tumor-like appearance but is considered to be a massive reactive lesion rather than a true neoplasia. Limited information about the pathogenesis of epulis is available. The purpose of our study was to identify potential signaling pathways in fibrous epulis through transcriptome profiling.
METHODS: Differentially expressed genes (DEGs) between fibrous epulis lesions and normal gingival tissues were detected using RNA sequencing (RNAseq). The expression levels of eighteen genes were validated using quantitative real-time PCR (qRT-PCR).
RESULTS: RNAseq identified 533 upregulated genes and 732 downregulated genes. The top 10 upregulated genes were IL11, OSM, MMP3, KRT75, MMP1, IL6, IL1B, IL24, SP7, and ADGRG3. The top 10 downregulated genes were BCHE, TYR, DCT, KRT222, RP11-507K12.1, COL6A5, PMP2, GFRA1, SCN7A, and CDH19. KEGG pathway analysis further indicated that the DEGs were enriched in \"Pathways in cancer\" and the \"Ras signaling pathway\". quantitative real-time PCR verified that the expression levels of SOS1, HRAS, PIK3CA, AKT3, IKBKA, IKBKB, NFKB1, BCL2, BCL2L1, XIAP, BIRC2, and BIRC3 were increased significantly.
CONCLUSIONS: The current transcriptomic profiling study reveals that in fibrous epulis, RAS-PI3K-AKT-NF-κB pathway transcriptionally regulates the expression of BCL2 family and IAP family genes, leading to increased proliferation and apoptosis inhibition.
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