Circular RNA circ-Foxo3 inhibits esophageal squamous cell cancer progression via the miR-23a/PTEN axis

J Cell Biochem. 2020 Mar;121(3):2595-2605. doi: 10.1002/jcb.29481. Epub 2019 Nov 3.

Abstract

Circ-Foxo3 is a circRNA encoded by the human FOXO3 gene and works as a sponge for potential microRNAs (miRNAs) to regulate cancer progression. However, the role of circ-Foxo3 in esophageal squamous cell cancer (ESCC) is not clear. In this study, circ-Foxo3 was lowly expressed in cell lines and ESCC tissues. Meanwhile, overexpression of circ-Foxo3 inhibited cell growth, migration, and invasion, whether in vivo or in vitro. Mechanically, we found a potential miRNA target, miR-23a, which negatively correlated with circ-Foxo3 in ESCC. Then, a luciferase assay confirmed the relationship between the circ-Foxo3 and miRNA. Moreover, circ-Foxo3 upregulation of PTEN occurred through "sponging" miR-23a. Taken together, these results indicated that the circ-Foxo3/miR-23a/PTEN pathway was critical for inhibiting the ESCC progression. This may provide a promising target for treat ESCC.

Keywords: PTEN; circ-Foxo3; esophageal squamous cell cancer; miR-23a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Forkhead Box Protein O3 / genetics
  • Forkhead Box Protein O3 / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Prognosis
  • RNA, Circular / genetics*
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • MIRN23a microRNA, human
  • MicroRNAs
  • RNA, Circular
  • PTEN Phosphohydrolase
  • PTEN protein, human