hsa_circRNA_100533 regulates GNAS by sponging hsa_miR_933 to prevent oral squamous cell carcinoma

J Cell Biochem. 2019 Nov;120(11):19159-19171. doi: 10.1002/jcb.29245. Epub 2019 Jul 11.

Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck region. Circular RNA (circRNA), as one kind of noncoding RNA, involves in biological processes in diverse cancers. circRNA functions mainly as the microRNA (miRNA) sponge, competitively binding to miRNAs to regulate target gene expressions. However, the expression profiles and roles of circRNAs in OSCC are still unexplored. circRNA microarrays and quantitative real-time polymerase chain reaction was used to identify the hsa_circRNA_100533 downregulated in OSCC tissues and cell lines. Bioinformatics methods were used to predict the interactions among circRNAs, miRNA, and target genes. Based on the luciferase reporter assay and AGO2 RIP assay, we found that hsa_circRNA_100533 binds to miRNAs as a miRNA sponge. hsa_circRNA_100533 inhibited cell proliferation, migration, and promoted cell apoptosis in OSCC cell lines, which could be blocked by hsa-miR-933 overexpression. hsa_circRNA_100533 binds to hsa-miR-933 as a miRNA sponge to regulate GNAS expression, and to modulate cell proliferation, migration, and apoptosis. In summary, the hsa_circRNA_100533-miR-933-GNAS axis affect the proliferation and apoptosis of OSCC cells through the mechanism of competing endogenous RNAs. hsa_circRNA_100533 may function as promising diagnostic biomarkers and effective therapeutic targets for OSCC.

Keywords: GNAS; OSCC; hsa-miR-933; hsa_circRNA_100533.

MeSH terms

  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Chromogranins / genetics
  • Chromogranins / metabolism*
  • GTP-Binding Protein alpha Subunits, Gs / genetics
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Nestin / genetics
  • Nestin / metabolism*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*

Substances

  • Chromogranins
  • MIRN193 microRNA, human
  • MicroRNAs
  • Nestin
  • RNA, Circular
  • RNA, Neoplasm
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs