J Gynecol Oncol.  2025 Jan;36(1):e11. 10.3802/jgo.2025.36.e11.

ATF1 regulates MAL2 expression through inhibition of miR-630 to mediate the EMT process that promotes cervical cancer cell development and metastasis

• Cao Y
• Peng Y
• Tang Y

• KMID: 2565439
• DOI: http://doi.org/10.3802/jgo.2025.36.e11

Abstract

Objective
The existence of activating transcription factor 1 (ATF1) could be employed as a clinical marker in the context of cervical cancer development, although its specific mechanism has not been fully clarified.
Methods
To evaluate the presence of ATF1, miR-630, and myelin and lymphocyte protein 2 (MAL2) in cervical malignancies, we conducted quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot assays; further studied the expansion, migration, invasion and epithelial-mesenchymal transition (EMT) of cervical carcinoma cells using colony formation assay, transwell, loss cytometry, Western blot. Chromatin immunoprecipitation (ChIP) and RNA immunoprecipitation (RIP) were used to verify that ATF1 could directly transcriptionally repress miR-630; dual luciferase reporter assay and RIP assay were employed to confirm that miR-630 targeted to repress MAL2.
Results
In cervical cancer cases, elevated ATF1 expression and reduced miR-630 expression were detected, displaying a negative relationship between them. Inhibition of ATF1 hindered the growth, migration, infiltration, and EMT in cervical carcinoma cells, while upregulation of miR-630 mitigated the aggressive characteristics of these cells. ATF1 was found to transcriptionally repress miR-630 by TransmiR and ALGGEN prediction and ChIP validation. MicroRNA modulates gene expression and affects cancer progression, and we discovered that miR-630 regulates cancer progression by targeting and inhibiting MAL2.
Conclusion
ATF1, which modulates the miR-630/MAL2 pathway, affects the EMT process and cervical carcinoma cell growth and spread. Therefore, ATF1 may serve as a promising marker and treatment target for cervical malignancies intervention.

Keyword

Cervical Cancer; Activating Transcription Factor 1; Epithelial-Mesenchymal Transition; Metastasis