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Carcinogenesis ; 44(6): 463-475, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37158456

RESUMO

Circular RNAs (circRNAs) have been accepted to play key roles in the development and progression of mutiple cancers including colorectal cancer (CRC). Here, we identified circ-METTL9, derived from 2 to 4 exons of METTL9 gene, may promote CRC progression by accelerating cell cycle progression. However, the role and mechanism of circ-METTL9 in CRC remains unclear. Based on our data, the expression of circ-METTL9 was significantly upregulated in CRC tissues and markedly increased in advanced tumors in CRC patients. Functional experiments demonstrated that circ-METTL9 overexpression promoted CRC cells proliferation and migration in vitro, and simultaneously enhanced CRC tumor growth and metastasis in vivo. Mechanistically, RNA immunoprecipitation (RIP) assays proved that circ-METTL9 might be a miRNA sponge, and RNA pulldown assays showed the interaction between circ-METTL9 and miR-551b-5p. Notably, cyclin-dependent kinase 6 (CDK6), a key regulator in cell cycle, is a conserved downstream target of miR-551b-5p. Taken together, our findings highlight a novel oncogenic function of circ-METTL9 in CRC progression via circ-METTL9/miR-551b-5p/CDK6 axis, which may serve as a prognostic biomarker and therapeutic target for CRC patients.


Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Quinase 6 Dependente de Ciclina/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Metiltransferases/metabolismo
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