国际妇产科学杂志

国际妇产科学杂志 ›› 2025, Vol. 52 ›› Issue (4): 414-419.doi: 10.12280/gjfckx.20250231

• 妇科肿瘤研究:综述 • 上一篇    下一篇

m6A甲基化修饰在子宫内膜癌中的研究进展

思彩霞, 程岳, 孙壬涟, 许飞雪△()   

  1. 730000 兰州大学第一临床医学院（思彩霞，程岳，孙壬涟）； 兰州大学第一医院妇产科（许飞雪）
  • 收稿日期:2025-03-10 出版日期:2025-08-15 发布日期:2025-09-08
  • 通讯作者: 许飞雪，E-mail：xfx.sxq@163.com
  • 作者简介:△审校者

Research Progress on m6A Methylation in Endometrial Cancer

SI Cai-xia, CHENG Yue, SUN Ren-lian, XU Fei-xue△()   

  1. The First School of Clinical Medicine of Lanzhou University, Lanzhou 730000, China (SI Cai-xia, CHENG Yue, SUN Ren-lian); Department of Obstetrics and Gynecology, The First Hospital of Lanzhou University, Lanzhou 730000, China (XU Fei-xue)
  • Received:2025-03-10 Published:2025-08-15 Online:2025-09-08
  • Contact: XU Fei-xue, E-mail: xfx.sxq@163.com

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摘要：

子宫内膜癌（endometrial cancer，EC）作为女性生殖系统三大恶性肿瘤之一，其发病率和死亡率在全球范围内呈上升趋势，早期患者预后良好，但晚期及复发性患者生存期显著缩短。N6-甲基腺苷（N6-methyladenosine，m6A）甲基化修饰是真核生物RNA中最丰富的表观转录组修饰，由甲基转移酶、去甲基化酶和甲基结合蛋白三类调节因子协同动态调控RNA代谢。研究表明，这些调节因子表达异常在EC的发病机制和疾病进展中发挥关键作用。例如，甲基转移酶样3（methyltransferase-like 3，METTL3）激活蛋白激酶B（protein kinase B，Akt）信号通路，Wilms肿瘤1相关蛋白（Wilms′ tumor 1-associating protein，WTAP）通过影响早期生长反应基因1（early growth response gene 1，EGR1）/PTEN通路增强EC干细胞的特性。脂肪量和肥胖相关蛋白（fat mass and obesity-associated protein，FTO）和AlkB同源物5（AlkB homolog 5，ALKBH5）分别通过磷脂酰肌醇3激酶（phosphoinositide 3-kinase，PI3K）/Akt等信号通路及调节胰岛素样生长因子1受体（insulin-like growth factor 1 receptor，IGF1R）表达，促进EC细胞增殖侵袭。此外，YTH m6A RNA结合蛋白2（YTH m6A RNA-binding protein 2，YTHDF2）和IGF2 mRNA结合蛋白（IGF2 mRNA binding protein，IGF2BP）也参与调控EC细胞恶性表型。这些发现为EC的早期诊断和精准治疗提供了新视角。诊疗方面，METTL3、METTL14、FTO等蛋白高表达提示不良预后，而YTHDF2是鉴别癌前病变的潜在标志物。此外，METTL3过表达可激活CD8+ T细胞，抑制EC增殖，而METTL3/FGD5-AS1轴介导紫杉醇耐药，为EC的免疫治疗和改善化疗耐药奠定了理论基础。

关键词: 甲基化, 子宫内膜肿瘤, 治疗, 疾病恶化, m6A甲基化, 发病机制

Abstract:

Endometrial cancer (EC), as one of the three major malignant tumors in the female reproductive system, shows an increasing trend in incidence and mortality globally. Patients with early-stage EC have a favorable prognosis, but the survival time of those with advanced-stage and recurrent EC is significantly shortened. N6-methyladenosine (m6A) methylation is the most abundant epitranscriptomic modification in eukaryotic RNA, and the metabolism of RNA is dynamically regulated by three types of regulatory factors: methyltransferases, demethylases, and m6A-binding proteins. Studies have shown that abnormal expression of these regulatory factors plays a critical role in the pathogenesis and progression of EC. For instance, methyltransferase like 3 (METTL3) activates the protein kinase B (Akt) signaling pathway, and Wilms′ tumor 1-associating protein (WTAP) enhances the characteristics of EC stem cells by affecting the early growth response gene 1 (EGR1)/PTEN pathway. Fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5) promote the proliferation and invasion of EC cells through signaling pathways such as phosphoinositide 3-kinase (PI3K)/Akt and by regulating the expression of insulin-like growth factor 1 receptor (IGF1R), respectively. In addition, YTH m6A RNA-binding protein 2 (YTHDF2) and IGF2 mRNA binding protein (IGF2BP) also participate in the regulation of the malignant phenotypes of EC cells. These findings provide novel perspectives for the early diagnosis and precise therapy of EC. In terms of diagnosis and treatment, high expression of proteins such as METTL3, METTL14, and FTO indicates a poor prognosis, while YTHDF2 is a potential biomarker for identifying precancerous lesions. Furthermore, overexpression of METTL3 can activate CD8+ T cells to inhibit the proliferation of EC, and the METTL3/FGD5-AS1 axis mediates paclitaxel resistance, which lays a theoretical foundation for the immunotherapy of EC and the improvement of chemotherapy resistance.

Key words: Methylation, Endometrial neoplasms, Therapy, Disease progression, m6A methylation, Pathogenesis