Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, P.R. China.
Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong, P.R. China.
FASEB J. 2024 Jun 15;38(11):e23693. doi: 10.1096/fj.202400580.
N6-methylated adenosine (mA) 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 mA 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 mA modification was observed in CC cells, targeting phosphodiesterase 3A (PDE3A). METTL3 catalyzed mA modification on PDE3A mRNA through YTH domain family protein 3 (YTHDF3). Our study indicated the mechanism of mA modification in CC and suggested the METTL3/YTHDF3/PDE3A axis as a potential clinical target for CC treatment.
N6-甲基腺苷（m6A）是真核生物中一种重要的 RNA 修饰，尤其在癌症中。然而，其在宫颈癌（CC）中的作用尚不清楚。我们旨在通过分析甲基转移酶样 3（METTL3）表达、鉴定下游靶点，并探讨潜在机制，阐明 m6A 在 CC 中的作用。我们使用 Western blot、定量聚合酶链反应（qPCR）和免疫组织化学评估了 CC 中 METTL3 的表达。体外和体内实验研究了 METTL3 在 CC 中的作用。我们采用 RNA 测序、m6A 免疫沉淀测序、qPCR 和 RNA 免疫沉淀 qPCR 来探讨 METTL3 在 CC 中的机制。METTL3 在 CC 中表达上调，促进细胞增殖和转移。METTL3 敲低通过抑制 AKT/mTOR 信号通路抑制人宫颈癌。在 CC 细胞中观察到 METTL3 介导的 m6A 修饰，靶向磷酸二酯酶 3A（PDE3A）。METTL3 通过 YTH 结构域家族蛋白 3（YTHDF3）催化 PDE3A mRNA 的 m6A 修饰。本研究揭示了 m6A 修饰在 CC 中的机制，并提示 METTL3/YTHDF3/PDE3A 轴可能成为 CC 治疗的潜在临床靶点。
