H3K27ac-induced FOXC2-AS1 accelerates tongue squamous cell carcinoma by upregulating E2F3

J Oral Pathol Med. 2021 Nov;50(10):1018-1030. doi: 10.1111/jop.13232. Epub 2021 Aug 17.

Abstract

Background: The important roles of lncRNAs have been reported in cancers, including tongue squamous cell carcinoma (TSCC). Here, we investigated the functional role and molecular mechanisms of lncRNA FOXC2-AS1 in TSCC.

Methods: The expression level of FOXC2-AS1 in TSCC was determined by RT-qPCR. Its biological role was evaluated through colony formation assay, flow cytometry, wound healing, transwell, and Western blot analyses. The interactions among gene were tested by mechanistic investigations.

Results: FOXC2-AS1 expression was high in TSCC tissues and cells. Functional assays in vitro showed that silencing FOXC2-AS1 restrained cell proliferation, cell cycle, migration, invasion, and EMT. In the mechanism, it was verified that H3K27 acetylation (H3K27ac) triggered an increase in FOXC2-AS1 expression. Furthermore, FOXC2-AS1 was identified as a cytoplasmic lncRNA and served as a ceRNA to upregulate E2F3 expression via sponging miR-6868-5p.

Conclusion: H3K27ac-induced FOXC2-AS1 exhibits carcinogenic property in TSCC by the miR-6868-5p/E2F3 axis.

Keywords: E2F3; FOXC2-AS1; histone acetylation; tongue squamous cell carcinoma.

MeSH terms

  • Acetylation
  • Carcinoma, Squamous Cell* / genetics
  • Cell Line, Tumor
  • E2F3 Transcription Factor
  • Forkhead Transcription Factors / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • RNA, Long Noncoding / genetics*
  • Tongue
  • Tongue Neoplasms* / genetics

Substances

  • E2F3 Transcription Factor
  • E2F3 protein, human
  • Forkhead Transcription Factors
  • MicroRNAs
  • RNA, Long Noncoding
  • mesenchyme fork head 1 protein