ATF1通过抑制miR-630来调节MAL2表达,介导促进宫颈癌细胞发育和转移的EMT过程。
ATF1 regulates MAL2 expression through inhibition of miR-630 to mediate the EMT process that promotes cervical cancer cell development and metastasis.
发表日期:2024 Jul 02
作者:
Yanming Cao, Yuping Peng, Youqun Tang
来源:
Journal of Gynecologic Oncology
摘要:
激活转录因子1(ATF1)的存在可以作为宫颈癌发展背景下的临床标志物,尽管其具体机制尚未完全阐明。评估ATF1、miR-630、髓磷脂和淋巴细胞的存在蛋白2(MAL2)在宫颈恶性肿瘤中的作用,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测定;利用集落形成实验、Transwell、丢失细胞术、Western blot等进一步研究了宫颈癌细胞的扩增、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)验证ATF1可以直接转录抑制miR-630;采用双荧光素酶报告基因检测和RIP检测证实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,两者呈负相关。 ATF1 的抑制阻碍了宫颈癌细胞的生长、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 可以转录抑制 miR-630。 MicroRNA调节基因表达并影响癌症进展,我们发现miR-630通过靶向和抑制MAL2来调节癌症进展。ATF1调节miR-630/MAL2通路,影响EMT过程和宫颈癌细胞的生长和扩散。因此,ATF1可能作为宫颈恶性肿瘤干预的一个有前途的标志物和治疗靶点。©2025。亚洲妇科肿瘤学会、韩国妇科肿瘤学会和日本妇科肿瘤学会。
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.© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.