Circular RNA ubiquitin-associated protein 2 enhances autophagy and promotes colorectal cancer progression and metastasis via miR-582-5p/FOXO1 signaling

J Genet Genomics. 2021 Dec;48(12):1091-1103. doi: 10.1016/j.jgg.2021.07.017. Epub 2021 Aug 18.

Abstract

Numerous circular RNAs (circRNAs) have been identified as vital regulators in various cancers. The newly reported circular RNA ubiquitin-associated protein 2 (circUBAP2) is a critical player in cell growth and metastasis in various types of cancers, although its role in colorectal cancer (CRC) has yet to be fully elucidated. We find that circUBAP2 is upregulated in CRC tissues and cell lines to induce autophagy both in vitro and in vivo. The effects of circUBAP2 on migration, invasion, and proliferation may be partially related to autophagy. Mechanistically, we uncover that circUBAP2 can directly interact with miR-582-5p and subsequently act as a microRNA sponge to regulate the expression of the miR-582-5p target gene forkhead box protein O1 (FOXO1) and downstream signaling molecules, which collectively advance the progression and metastasis of CRC. These results suggest that circUBAP2 acts as an oncogene via a novel circUBAP2/miR-582-5p/FOXO1 axis, providing a potential biomarker and therapeutic target for CRC management.

Keywords: Autophagy; CircUBAP2; Colon cancer; FOXO1; MiR-582-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / pathology
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics
  • Ubiquitin / genetics
  • Ubiquitin / metabolism

Substances

  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • MIRN582 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Ubiquitin