METTL3's role in cervical cancer development through m6A modification

• Published in: The FASEB journal Vol. 38; no. 11
• Main Authors: Liu, Yuqiu, Li, Changzhong, Deng, Qianqian, Ren, Xingye, Wang, Hongqing
• Format: Journal Article
• Language: English
• Published: 15.06.2024
• Subjects: cervical cancer; methyltransferase‐like 3; N6‐methylated adenosine; phosphodiesterase 3A; YTH domain family protein 3
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.202400580

N6‐methylated adenosine (m6A) is a crucial RNA modification in eukaryotes, particularly in cancer. However, its role in cervical cancer (CC) is unclear. We aimed to elucidate the part of m6A in CC by analyzing methyltransferase‐like 3 (METTL3) expression, identifying downstream targets, and exploring the underlying mechanism. We assessed METTL3 expression in CC using western blotting, quantitative polymerase chain reaction (qPCR), and immunohistochemistry. In vitro and in vivo experiments examined METTL3's role in CC. We employed RNA sequencing, methylated RNA immunoprecipitation sequencing, qPCR, and RNA immunoprecipitation qPCR to explore METTL3's mechanism in CC. METTL3 expression was upregulated in CC, promoting cell proliferation and metastasis. METTL3 knockdown inhibited human cervical cancer by inactivating AKT/mTOR signaling pathway. METTL3‐mediated m6A modification was observed in CC cells, targeting phosphodiesterase 3A (PDE3A). METTL3 catalyzed m6A modification on PDE3A mRNA through YTH domain family protein 3 (YTHDF3). Our study indicated the mechanism of m6A modification in CC and suggested the METTL3/YTHDF3/PDE3A axis as a potential clinical target for CC treatment. Methyltransferase like 3 (METTL3) expression was upregulated in cervical cancer, promoting cell proliferation and metastasis. METTL3 knockdown inhibited human cervical cancer by inactivating AKT/mTOR signaling pathway. METTL3‐mediated m6A modification was observed in cervical cancer cells, targeting phosphodiesterase 3A (PDE3A). METTL3 catalyzed m6A modification on PDE3A mRNA through YTH domain family protein 3 (YTHDF3).