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

  • Am J Med Sci. 2025 Mar 8:S0002-9629(25)00950-4. doi: 10.1016/j.amjms.2025.03.002.
Zhuyun Ding  1 ,  Lirong Fu  2 ,  Qian Zhu  3 ,  Shu Bian  4 ,  Min Cui  5 ,  Yan Li  6 ,  Xiaoyan Ying  7
Affiliations
  • 1. 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.
  • 2. Department of Obstetrics and Gynecology,Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China.
  • 3. Department of Obstetrics and Gynecology, the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, 211100, China.
  • 4. Department of Infection,Shanghai Songjiang Clinical College of Nanjing Medical University,Nanjing, 211100, China.
  • 5. Medical Department,Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China.
  • 6. Songjiang research Institute and Songjiang Hospital, Department of Anatomy and Physiology, College of Basic Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China. Electronic address: [email protected].
  • 7. Department of Obstetrics and Gynecology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu Province, China. Electronic address: [email protected].
PMID: 40064293 DOI: 10.1016/j.amjms.2025.03.002
Abstract

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. 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.

Keywords
ALKBH5; Cell migration; Cell proliferation; Uterine corpus endometrial carcinoma; ceRNA; m6A.
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