Ding Zhuyun, Fu Lirong, Zhu Qian, Bian Shu, Cui Min, Li Yan, Ying Xiaoyan
Department of Obstetrics and Gynecology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu Province, China; Department of Obstetrics and Gynecology,Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China.
Department of Obstetrics and Gynecology,Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China.
Am J Med Sci. 2025 Jun;369(6):726-738. doi: 10.1016/j.amjms.2025.03.002. Epub 2025 Mar 8.
Uterine corpus endometrial carcinoma (UCEC) is one of the most common gynecological malignancies, with an annually increasing incidence and a poor prognosis. lncRNAs and microRNAs regulate the progression of UCEC through ceRNA networks. Additionally, m6A modification plays various roles in UCEC, and abnormal regulation of it can directly affect tumor progression. However, the role of m6A-associated ceRNA networks in UCEC remains unclear.
Bioinformatics methods were used to construct the ceRNA regulatory network of m6A related genes in UCEC. MeRIP assays, dual-luciferase reporter assays and other experiments were used to prove the conclusions.
This study showed that the AC074117.1/miR-193a-3p axis promoted the malignant progression of UCEC through ALKBH5, an m6A demethylase. MeRIP assay indicated that ALKBH5 regulated m6A modification in UCEC. Gene set enrichment analysis and cell proliferation and migration assays showed that the AC074117.1/miR-193a-3p/ALKBH5 axis regulated the proliferation and migration of UCEC cells. With regard to mechanistic analysis, dual-luciferase reporter assay demonstrated that AC074117.1 acted as a ceRNA for miR-193a-3p, influencing the expression of ALKBH5. Furthermore, rescue experiments validated that the regulatory effects of miR-193a-3p on the malignant progression of UCEC relied on ALKBH5 to some extent.
Altogether, this study revealed an m6A-related ceRNA network in UCEC, which may serve as a target for early diagnosis and treatment.
子宫内膜癌（UCEC）是最常见的妇科恶性肿瘤之一，发病率逐年上升且预后较差。长链非编码RNA（lncRNAs）和微小RNA（microRNAs）通过竞争性内源RNA（ceRNA）网络调节UCEC的进展。此外，N6-甲基腺嘌呤（m6A）修饰在UCEC中发挥多种作用，其异常调控可直接影响肿瘤进展。然而，m6A相关ceRNA网络在UCEC中的作用仍不清楚。
采用生物信息学方法构建UCEC中m6A相关基因的ceRNA调控网络。运用甲基化RNA免疫沉淀法（MeRIP）、双荧光素酶报告基因检测法等实验来验证研究结果。
本研究表明，AC074117.1/miR-193a-3p轴通过m6A去甲基化酶ALKBH5促进UCEC的恶性进展。MeRIP检测表明ALKBH5调节UCEC中的m6A修饰。基因集富集分析以及细胞增殖和迁移实验表明，AC074117.1/miR-193a-3p/ALKBH5轴调节UCEC细胞的增殖和迁移。在机制分析方面，双荧光素酶报告基因检测表明AC074117.1作为miR-193a-3p的ceRNA，影响ALKBH5的表达。此外，挽救实验证实miR-193a-3p对UCEC恶性进展的调控作用在一定程度上依赖于ALKBH5。
总之，本研究揭示了UCEC中一个与m6A相关的ceRNA网络，其可能成为早期诊断和治疗的靶点。
