Cao Yanming, Peng Yuping, Tang Youqun
Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, China.
J Gynecol Oncol. 2025 Jan;36(1):e11. doi: 10.3802/jgo.2025.36.e11. Epub 2024 Jul 2.
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.
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.
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.
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.
激活转录因子1（ATF1）的存在可作为宫颈癌发生背景下的一种临床标志物，尽管其具体机制尚未完全阐明。
为评估ATF1、miR-630和髓鞘与淋巴细胞蛋白2（MAL2）在宫颈恶性肿瘤中的存在情况，我们进行了定量逆转录聚合酶链反应、免疫组织化学和蛋白质印迹分析；使用集落形成试验、Transwell小室实验、流式细胞术、蛋白质印迹进一步研究宫颈癌细胞的增殖、迁移、侵袭和上皮-间质转化（EMT）。采用染色质免疫沉淀（ChIP）和RNA免疫沉淀（RIP）来验证ATF1可直接转录抑制miR-630；采用双荧光素酶报告基因检测和RIP检测来确认miR-630靶向抑制MAL2。
在宫颈癌病例中，检测到ATF1表达升高和miR-630表达降低，二者呈负相关。抑制ATF1可阻碍宫颈癌细胞的生长、迁移、浸润和EMT，而miR-630的上调则减轻了这些细胞的侵袭性特征。通过TransmiR和ALGGEN预测以及ChIP验证发现ATF1可转录抑制miR-630。微小RNA调节基因表达并影响癌症进展，我们发现miR-630通过靶向抑制MAL2来调节癌症进展。
调节miR-630/MAL2通路的ATF1影响EMT过程以及宫颈癌细胞的生长和扩散。因此，ATF1可能是宫颈恶性肿瘤干预的一个有前景的标志物和治疗靶点。
