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

• Published in: Carcinogenesis (New York) Vol. 44; no. 6; pp. 463 - 475
• Main Authors: Li, Ming, Zhi, Zheng, Jiang, Xuan, Duan, Guo-Cai, Zhu, Wei-Na, Pang, Zheng, Wang, Lian, Ge, Rui, Dai, Xin, Liu, Jia-Meng, Chen, Ting-Yue, Jia, Jin-Jing, Li, Jian-Ming, Sun, Li-Na
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 18.08.2023
• Subjects: miRNA sponge; Circular RNA; cell cycle; Colorectal cancer
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgad031

Abstract 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. Graphical Abstract Graphical Abstract