Circular RNA circCTNNA1 promotes colorectal cancer progression by sponging miR-149-5p and regulating FOXM1 expression

Cell Death Dis. 2020 Jul 22;11(7):557. doi: 10.1038/s41419-020-02757-7.

Abstract

Circular RNAs (circRNAs) are an emerging class of non-coding RNAs, identified to participate in multiple malignancies. Nevertheless, the clinical significance, biological function, and regulatory mechanisms of circRNAs in colon cancer (CC) remain largely unclear. In this study, the circRNA expression profile in CC and matched normal tissues was analyzed using circRNA microarrays. A novel circRNA, circCTNNA1, was significantly upregulated in CC, and its level was associated with advanced tumor-node-metastasis stage and poor prognosis of patients with CC. Functional experiments, including Cell Counting Kit-8, colony formation, 5-ethynyl-2'-deoxyuridine, transwell, wound healing, flow cytometric analysis, and in vivo tumorigenesis assay were then performed to investigate the oncogenic role of circCTNNA1. The results revealed that circCTNNA1 promoted CC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, RNA pull-down, RNA immunoprecipitation, dual-luciferase reporter assays, and fluorescent in situ hybridization were performed to unveil that circCTNNA1 can serve as a competing endogenous RNA of miR-149-5p to counteract the suppressive effect of miR-149-5p on downstream target Forkhead Box M1 (FOXM1). In summary, our study demonstrated that circCTNNA1 facilitated CC proliferation and invasion via the circCTNNA1/miR-149-5p/FOXM1 axis, and it might function as a novel diagnostic or therapeutic target for patients with CC.

MeSH terms

  • Aged
  • Animals
  • Base Sequence
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA, Neoplasm / biosynthesis
  • Disease Progression*
  • Female
  • Forkhead Box Protein M1 / genetics
  • Forkhead Box Protein M1 / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Survival Analysis
  • Up-Regulation / genetics

Substances

  • DNA, Neoplasm
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • MIRN149 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Messenger