METTL9 derived circular RNA circ-METTL9 sponges miR-551b-5p to accelerate colorectal cancer progression by upregulating CDK6

Autor: Ming Li, Zheng Zhi, Xuan Jiang, Guo-Cai Duan, Wei-Na Zhu, Zheng Pang, Lian Wang, Rui Ge, Xin Dai, Jia-Meng Liu, Ting-Yue Chen, Jin-Jing Jia, Jian-Ming Li, Li-Na Sun
Rok vydání: 2023
Předmět:
Zdroj: Carcinogenesis.
ISSN: 1460-2180
0143-3334
DOI: 10.1093/carcin/bgad031
Popis: 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 2-4 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.
Databáze: OpenAIRE