Methyltransferase-like 3 (METTL3) functions as an RNA methyltransferase that controls the modification of N(6)-methyladenosine (m6A) to influence the biosynthesis, decay, and translation of mRNAs. This study aims to investigate the regulation of METTL3-mediated promotion of microRNA-126-5p (miR-126-5p) in the progression of ovarian cancer and to identify the mechanisms in relation to phosphatase and tensin homolog (PTEN) and the PI3K/Akt/mTOR pathway. We found high expression of miR-126-5p in ovarian cancer samples compared to paired adjacent samples, and also in ovarian cancer cell lines. Gain-of-function experiments demonstrated that overexpression of miR-126-5p promoted ovarian cancer cell proliferation, migration, and invasion, and inhibited their apoptosis. Luciferase reporter assay identified that miR-126-5p could directly bind to PTEN. By targeting PTEN, miR-126-5p could activate the PI3K/Akt/mTOR pathway. Furthermore, the RNA methyltransferase METTL3 promoted the maturation of miR-126-5p via the m6A modification of pri-miR-126-5p. Finally, in vitro and in vivo experiments substantiated that silencing of METTL3 impeded the progression and tumorigenesis of ovarian cancer by impairing the miR-126-5p-targeted inhibition of PTEN and thus blocking the PI3K/Akt/mTOR pathway. Coherently, knockdown of METTL3 inhibited the effect of miR-126-5p to upregulate PTEN, and thus prevents PI3K/Akt/mTOR pathway activation, thereby suppressing the development of ovarian cancer. These findings highlight potential targets for the future ovarian cancer treatment as well as tumorigenic mechanisms mediated by m6A modification.

甲基转移酶样 3 (METTL3) 作为 RNA 甲基转移酶发挥作用，控制N的修饰(6)-甲基腺苷 (m6A) 影响 mRNA 的生物合成、衰变和翻译。本研究旨在探讨 METTL3 介导的 microRNA-126-5p (miR-126-5p) 在卵巢癌进展中的调控作用，并确定与磷酸酶和张力蛋白同源物 (PTEN) 和 PI3K/ Akt/mTOR 通路。与配对的相邻样本相比，我们发现 miR-126-5p 在卵巢癌样本中以及在卵巢癌细胞系中的高表达。功能获得实验表明，过表达 miR-126-5p 可促进卵巢癌细胞增殖、迁移和侵袭，并抑制其凋亡。荧光素酶报告基因分析发现 miR-126-5p 可以直接与 PTEN 结合。通过靶向 PTEN，miR-126-5p 可以激活 PI3K/Akt/mTOR 通路。此外，RNA甲基转移酶METTL3通过pri-miR-126-5p的m6A修饰促进了miR-126-5p的成熟。最后，体外和体内实验证实，METTL3 的沉默通过削弱 PTEN 的 miR-126-5p 靶向抑制并因此阻断 PI3K/Akt/mTOR 通路来阻碍卵巢癌的进展和肿瘤发生。一致地，METTL3 的敲低抑制了 miR-126-5p 上调 PTEN 的作用，从而阻止了 PI3K/Akt/mTOR 通路的激活，从而抑制了卵巢癌的发展。这些发现突出了未来卵巢癌治疗的潜在靶点以及 m6A 修饰介导的致瘤机制。体外和体内实验证实，METTL3 的沉默通过削弱 miR-126-5p 靶向抑制 PTEN 从而阻断 PI3K/Akt/mTOR 通路来阻碍卵巢癌的进展和肿瘤发生。一致地，METTL3 的敲低抑制了 miR-126-5p 上调 PTEN 的作用，从而阻止了 PI3K/Akt/mTOR 通路的激活，从而抑制了卵巢癌的发展。这些发现突出了未来卵巢癌治疗的潜在靶点以及 m6A 修饰介导的致瘤机制。体外和体内实验证实，METTL3 的沉默通过削弱 miR-126-5p 靶向抑制 PTEN 从而阻断 PI3K/Akt/mTOR 通路来阻碍卵巢癌的进展和肿瘤发生。一致地，METTL3 的敲低抑制了 miR-126-5p 上调 PTEN 的作用，从而阻止了 PI3K/Akt/mTOR 通路的激活，从而抑制了卵巢癌的发展。这些发现突出了未来卵巢癌治疗的潜在靶点以及 m6A 修饰介导的致瘤机制。从而阻止 PI3K/Akt/mTOR 通路激活，从而抑制卵巢癌的发展。这些发现突出了未来卵巢癌治疗的潜在靶点以及 m6A 修饰介导的致瘤机制。从而阻止 PI3K/Akt/mTOR 通路激活，从而抑制卵巢癌的发展。这些发现突出了未来卵巢癌治疗的潜在靶点以及 m6A 修饰介导的致瘤机制。