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ZBTB24（锌指和 BTB 结构域蛋白 24）通过促进滋养细胞增殖、分化和迁移来防止复发性自然流产。

ZBTB24 (Zinc Finger and BTB Domain Containing 24) prevents recurrent spontaneous abortion by promoting trophoblast proliferation, differentiation and migration.

机构信息

Department of Obstetrics and Gynecology, The First People's Hospital of Wenling, Wenling, Zhejiang, China.

出版信息

Bioengineered. 2022 Feb;13(2):2777-2790. doi: 10.1080/21655979.2021.2019655.

DOI:10.1080/21655979.2021.2019655
PMID:35038951
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8973579/
Abstract

Recurrent spontaneous abortion (RSA) is a common complication during early gestation, which is associated with aberrant DNA methylation. Zinc Finger and BTB Domain Containing 24 (ZBTB24) plays a critical role in facilitating DNA methylation and cell proliferation. However, the regulatory role of ZBTB24 on trophoblast development in RSA remains unclear. In this study, ZBTB24 expression was compared between decidua tissues of RSA patients and induced abortion controls from a published dataset, which was further validated in placental villi tissues by RT-qPCR and Western blot. The roles of ZBTB24 in trophoblast proliferation, differentiation, and migration were investigated by functional assays after ZBTB24 knockdown or overexpression in HTR-8/SVneo cells. Our results showed that ZBTB24 expression was significantly decreased in RSA patients, and ZBTB24 expression level positively regulated cell viability, differentiation, and migration in HTR-8/SVneo cells. We further demonstrated that ZBTB24 modulated the expression of E-cadherin by altering the DNA methylation at the promoter region. Overall, the downregulation of ZBTB24 is implicated in RSA by inhibiting trophoblast proliferation, differentiation, and migration. Therefore, ZBTB24 may serve as a promising therapeutic target and diagnostic marker for RSA.

摘要

复发性自然流产（RSA）是妊娠早期的一种常见并发症，与异常的 DNA 甲基化有关。锌指和 BTB 结构域包含 24 个（ZBTB24）在促进 DNA 甲基化和细胞增殖中起着关键作用。然而，ZBTB24 对 RSA 中滋养层发育的调节作用尚不清楚。在这项研究中，我们比较了 RSA 患者和流产对照组的蜕膜组织中 ZBTB24 的表达，这一结果在胎盘绒毛组织中通过 RT-qPCR 和 Western blot 得到了进一步验证。通过在 HTR-8/SVneo 细胞中敲低或过表达 ZBTB24 后进行功能测定，研究了 ZBTB24 对滋养层增殖、分化和迁移的作用。我们的结果表明，ZBTB24 在 RSA 患者中的表达显著降低，并且 ZBTB24 的表达水平可正向调节 HTR-8/SVneo 细胞中的细胞活力、分化和迁移。我们进一步证明，ZBTB24 通过改变启动子区域的 DNA 甲基化来调节 E-钙黏蛋白的表达。总之，ZBTB24 的下调通过抑制滋养层的增殖、分化和迁移参与 RSA 的发生。因此，ZBTB24 可能作为 RSA 的有前途的治疗靶点和诊断标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/9091d9a89d1f/KBIE_A_2019655_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/ceffe3821d0f/KBIE_A_2019655_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/86ff61d14a63/KBIE_A_2019655_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/c60b72b933ca/KBIE_A_2019655_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/cea71c3f057c/KBIE_A_2019655_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/c6ab5460319f/KBIE_A_2019655_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/9091d9a89d1f/KBIE_A_2019655_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/ceffe3821d0f/KBIE_A_2019655_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/86ff61d14a63/KBIE_A_2019655_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/c60b72b933ca/KBIE_A_2019655_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/cea71c3f057c/KBIE_A_2019655_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/c6ab5460319f/KBIE_A_2019655_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e3/8973579/9091d9a89d1f/KBIE_A_2019655_F0006_OC.jpg

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