The RAS-PI3K-AKT-NF-κB pathway transcriptionally regulates the expression of BCL2 family and IAP family genes and inhibits apoptosis in fibrous epulis

J Clin Lab Anal. 2020 Mar;34(3):e23102. doi: 10.1002/jcla.23102. Epub 2019 Nov 19.

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.

Keywords: BCL2 family; RAS-PI3K-AKT-NF-κB pathway; RNA sequencing; apoptosis; fibrous epulis.

MeSH terms

  • Apoptosis / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Ontology
  • Gingiva / pathology
  • Gingival Diseases / genetics*
  • Gingival Diseases / pathology*
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / 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*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reproducibility of Results
  • Signal Transduction* / genetics
  • Transcription, Genetic*
  • ras Proteins / metabolism

Substances

  • Inhibitor of Apoptosis Proteins
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-akt
  • ras Proteins