Circular RNA circCTNNA1 promotes colorectal cancer progression by sponging miR-149-5p and regulating FOXM1 expression
Open Access
- 22 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (7), 1-12
- https://doi.org/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.Keywords
This publication has 31 references indexed in Scilit:
- Is “watch-and-wait” after chemoradiotherapy safe in patients with rectal cancer?BMJ, 2018
- Circular RNA YAP1 inhibits the proliferation and invasion of gastric cancer cells by regulating the miR-367-5p/p27 Kip1 axisMolecular Cancer, 2018
- Long non-coding RNA CCAL/miR-149/FOXM1 axis promotes metastasis in gastric cancerCell Death & Disease, 2018
- FoxM1 repression during human aging leads to mitotic decline and aneuploidy-driven full senescenceNature Communications, 2018
- Circular RNA circMTO1 acts as the sponge of microRNA‐9 to suppress hepatocellular carcinoma progressionJournal of Hepatology, 2017
- Noncoding Effects of Circular RNA CCDC66 Promote Colon Cancer Growth and MetastasisCancer Research, 2017
- An α‐E‐catenin (CTNNA1) mutation in hereditary diffuse gastric cancerThe Journal of Pathology, 2012
- clusterProfiler: an R Package for Comparing Biological Themes Among Gene ClustersOMICS: A Journal of Integrative Biology, 2012
- A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?Cell, 2011