AC074117.1/miR-193a-3p轴通过m6a相关基因ALKBH5调控子宫体子宫内膜癌的恶性进展。

IF 2.3 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

American Journal of the Medical Sciences Pub Date : 2025-06-01 DOI:10.1016/j.amjms.2025.03.002

Zhuyun Ding M.Sc , Lirong Fu M.Sc , Qian Zhu M.Sc , Shu Bian B.Sc , Min Cui B.Sc , Yan Li Ph.D , Xiaoyan Ying Ph.D

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引用次数: 0

摘要

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，预后较差。lncRNA和microRNA通过ceRNA网络调控UCEC的进展。此外，m6A修饰在UCEC中发挥着多种作用，其异常调控可直接影响肿瘤的进展。然而，m6A相关的ceRNA网络在UCEC中的作用仍不清楚。本研究表明，AC074117.1/miR-193a-3p轴通过m6A去甲基化酶ALKBH5促进了UCEC的恶性进展。MeRIP分析表明，ALKBH5调控UCEC中的m6A修饰。基因组富集分析和细胞增殖与迁移实验表明，AC074117.1/miR-193a-3p/ALKBH5轴调控了UCEC细胞的增殖和迁移。在机理分析方面，双荧光素酶报告实验表明，AC074117.1作为miR-193a-3p的ceRNA，影响了ALKBH5的表达。此外，拯救实验也验证了 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，这项研究揭示了 UCEC 中与 m6A 相关的 ceRNA 网络，可作为早期诊断和治疗的靶点。

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AC074117.1/miR-193a-3p axis regulates the malignant progression of uterine corpus endometrial carcinoma via the m6A-related gene ALKBH5

Introduction

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.

Methods

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.

Results

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.

Conclusions

Altogether, this study revealed an m6A-related ceRNA network in UCEC, which may serve as a target for early diagnosis and treatment.

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来源期刊

American Journal of the Medical Sciences 医学-医学：内科

CiteScore

4.40

自引率

0.00%

发文量

303

审稿时长

1.5 months

期刊介绍： The American Journal of The Medical Sciences (AJMS), founded in 1820, is the 2nd oldest medical journal in the United States. The AJMS is the official journal of the Southern Society for Clinical Investigation (SSCI). The SSCI is dedicated to the advancement of medical research and the exchange of knowledge, information and ideas. Its members are committed to mentoring future generations of medical investigators and promoting careers in academic medicine. The AJMS publishes, on a monthly basis, peer-reviewed articles in the field of internal medicine and its subspecialties, which include: Original clinical and basic science investigations Review articles Online Images in the Medical Sciences Special Features Include: Patient-Centered Focused Reviews History of Medicine The Science of Medical Education.