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. 2024 Jun 15;38(11):e23693.
doi: 10.1096/fj.202400580.

METTL3's role in cervical cancer development through m6A modification

Yuqiu Liu  1   2   3 , Changzhong Li  4 , Qianqian Deng  5 , Xingye Ren  6 , Hongqing Wang  1   2   3
Affiliations

METTL3's role in cervical cancer development through m6A modification

Yuqiu Liu et al. FASEB J. .

Abstract

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.

Keywords: N6‐methylated adenosine; YTH domain family protein 3; cervical cancer; methyltransferase‐like 3; phosphodiesterase 3A.

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