CircATIC inhibits esophageal carcinoma progression and promotes radiosensitivity by elevating RHCG through sponging miR-10-3p

Thorac Cancer. 2022 Apr;13(7):934-946. doi: 10.1111/1759-7714.14326. Epub 2022 Mar 20.

Abstract

Background: Circular RNAs (circRNAs) are implicated in the progression and radiosensitivity of human cancers, including esophageal carcinoma (ESCA). In this study, we aimed to explore the functions of circRNA 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (circATIC) in ESCA progression.

Methods: CircATIC expression, miR-10b-3p and Rh family C glycoprotein (RHCG) were examined via quantitative real-time polymerase chain reaction (qRT-PCR), western blot assay or immunohistochemistry (IHC) assay. 5'-ethynyl-2'-deoxyuridine (EdU), wound-healing, transwell, and cell colony formation assays and flow cytometry analysis were conducted to evaluate cell proliferation, migration, invasion, radiosensitivity and apoptosis, respectively. Dual-luciferase reporter assay and RNA pulldown assay were conducted to analyze the relationships among circATIC, miR-10b-3p and RHCG. A murine xenograft model assay was performed to explore the functions of circATIC in tumor formation and radiosensitivity in vivo.

Results: CircATIC was decreased in ESCA. CircATIC overexpression suppressed cell proliferation, migration and invasion and promoted radiosensitivity and apoptosis in ESCA cells in vitro and repressed tumor formation and radioresistance in vivo. Functionally, circATIC served as the sponge for miR-10b-3p, which directly targeted RHCG. MiR-10b-3p elevation reversed circATIC-mediated effect on ESCA cell progression. Moreover, miR-10b-3p inhibition suppressed cell growth and metastasis and enhanced radiosensitivity in ESCA cells by targeting RHCG.

Conclusions: Overexpression of circATIC hampered ESCA progression and promoted radiosensitivity depending on the regulation of miR-10b-3p and RHCG.

Keywords: ESCA; RHCG; circATIC; miR-10b-3p.

MeSH terms

  • Animals
  • Carcinoma*
  • Cation Transport Proteins*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Membrane Glycoproteins / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics
  • Radiation Tolerance / genetics

Substances

  • Cation Transport Proteins
  • Membrane Glycoproteins
  • MicroRNAs
  • RHCG protein, human
  • RNA, Circular
  • Rhcg protein, mouse