EIF4A3-negatively driven circular RNA ß-catenin (circß-catenin) promotes colorectal cancer progression via miR-197-3p/CTNND1 regulatory axis.
Br J Cancer
; 130(9): 1517-1528, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38459187
ABSTRACT
BACKGROUND:
Circß-catenin, our first reported circRNA, has been reported to mediate tumorigenesis in various cancers. However, its biological functions and underlying mechanisms in colorectal cancer (CRC) remain unknown.METHODS:
The qRT-PCR examination was used to detect the expression of circß-catenin, miR-197-3p, and CTNND1 in cells and human tissues. Western blot was conducted to detect the protein expression levels. The biological function of circß-catenin was verified by MTT, colony formation, wound healing, and transwell assays. The in vivo effects of circß-catenin were verified by nude mice xenograft and metastasis models. The regulatory network of circß-catenin/miR-197-3p/CTNND1 was confirmed via dual-luciferase reporter and RIP assays.RESULTS:
In the present study, circß-catenin was found to promote CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, circß-catenin served as miRNA decoy to directly bind to miR-197-3p, then antagonized the repression of the target gene CTNND1, and eventually promoted the malignant phenotype of CRC. More interestingly, the inverted repeated Alu pairs termed AluJb1/2 and AluY facilitated the biogenesis of circß-catenin, which could be partially reversed by EIF4A3 binding to Alu element AluJb2.CONCLUSIONS:
Our findings illustrated a novel mechanism of circß-catenin in modulating CRC tumorigenesis and metastasis, which provides a potential therapeutic target for CRC patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article