Department of Obstetrics, Affiliated Hospital of Weifang Medical University, Weifang, China.
Kaohsiung J Med Sci. 2019 Feb;35(2):87-94. doi: 10.1002/kjm2.12013.
Recurrent miscarriage (RM) affects about 1% of couples; however, the etiologies of half of the cases remain unknown. P53, a negative cell cycle regulator, has been found to modulate the expression of several long noncoding RNAs (lncRNAs) and overexpressed p53 has been observed in RM patients. To investigate the relationship between p53 and lncRNAs in the pathogenesis of RM, we detected the expression of p53 and six candidate lncRNAs in the villous from 27 RM patients and paired healthy controls. We found the level of NEAT1 and MALAT1 was reduced significantly and only the MALAT1 level negatively correlated with p53 protein level. By luciferase assay, we confirmed that p53 repress MALAT1 expression through directly binding to the promoter region. Functional study by using human trophoblast cell HTR-8/SVneo, we observed that p53 overexpression lead to decreased cells proliferation, migration, invasion and increased apoptosis. Meanwhile, MALAT1 overexpression partially restored these function of p53 overexpression.
复发性流产（RM）影响约 1%的夫妇；然而，一半病例的病因仍不清楚。p53 是一种负细胞周期调节剂，已被发现调节几种长链非编码 RNA（lncRNA）的表达，并且在 RM 患者中观察到过表达的 p53。为了研究 p53 和 lncRNA 在 RM 发病机制中的关系，我们检测了 27 例 RM 患者和配对健康对照组绒毛中 p53 和 6 个候选 lncRNA 的表达。我们发现 NEAT1 和 MALAT1 的水平显著降低，只有 MALAT1 水平与 p53 蛋白水平呈负相关。通过荧光素酶测定，我们证实 p53 通过直接结合启动子区域来抑制 MALAT1 的表达。通过使用人滋养层细胞 HTR-8/SVneo 进行功能研究，我们观察到 p53 过表达导致细胞增殖、迁移、侵袭减少，凋亡增加。同时，MALAT1 过表达部分恢复了 p53 过表达的这些功能。
