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

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 expressio...

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Bibliographic Details
Published in:Cell death & disease 2020-07, Vol.11 (7), p.557, Article 557
Main Authors: Chen, Pengju, Yao, Yunfeng, Yang, Nan, Gong, Lifei, Kong, Yuanyuan, Wu, Aiwen
Format: Article
Language:English
Subjects:
Aged
Animals
Apoptosis
Base Sequence
Carcinogenesis - genetics
Carcinogenesis - pathology
Cell cycle
Cell Cycle Checkpoints - genetics
Cell growth
Cell Line, Tumor
Cell migration
Cell Movement - genetics
Cell proliferation
Cell Proliferation - genetics
Circular RNA
Colon cancer
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Disease Progression
DNA, Neoplasm - biosynthesis
Female
Flow cytometry
Fluorescence in situ hybridization
Forkhead Box Protein M1 - genetics
Forkhead Box Protein M1 - metabolism
Forkhead protein
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Immunoprecipitation
Male
Maternal & child health
Medical prognosis
Medical screening
Metastases
Metastasis
Mice, Inbred BALB C
Mice, Nude
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
Neoplasm Invasiveness
Non-coding RNA
Ribonucleic acid
RNA
RNA, Circular - genetics
RNA, Circular - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Survival Analysis
Therapeutic applications
Tumorigenesis
Up-Regulation - genetics
Wound healing
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Summary: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.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-020-02757-7