This study aimed to investigate the mechanism by which MALAT1 regulates CRY2 expression and participates in trophoblast migration and invasion. Three patients with unexplained recurrent spontaneous abortion, four patients with missed abortion, and four women who underwent artificial miscarriages were enrolled in this study. Quantitative reverse‐transcription polymerase chain reaction and western blot analysis were used to detect RNA and protein expression, respectively. Trophoblast migration and invasion were detected by wound‐healing and transwell invasion assays. RNA pull‐down and Co‐IP assays were used to indicate the interaction between MALAT1 and FBXW7 or the interaction between FBXW7 and CRY2. The results showed significantly decreased MALAT1 expression in the villous specimens from the RSA patients relative to that in the villous specimens from the missed abortion patients and the normal villous specimens. MALAT1 promoted trophoblast cell migration and invasion by negatively regulating CRY2 protein expression. MALAT1 recruited FBXW7 to impair CRY2 protein stability. In conclusion, MALAT1 downregulation in trophoblasts might be related to miscarriage. MALAT1 may recruit the E3 ubiquitin ligase FBXW7 to induce CRY2 ubiquitin‐mediated degradation and participate in trophoblast migration and invasion.

中文翻译：

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MALAT1 招募 E3 泛素连接酶 FBXW7 来诱导 CRY2 泛素介导的降解并参与滋养层迁移和侵袭。

本研究旨在探讨 MALAT1 调节 CRY2 表达并参与滋养层迁移和侵袭的机制。本研究招募了 3 名不明原因复发性自然流产患者、4 名漏产患者和 4 名接受人工流产的女性。分别使用定量逆转录聚合酶链反应和蛋白质印迹分析检测 RNA 和蛋白质表达。通过伤口愈合和跨孔侵袭试验检测滋养细胞迁移和侵袭。RNA pull-down 和 Co-IP 测定用于指示 MALAT1 和 FBXW7 之间的相互作用或 FBXW7 和 CRY2 之间的相互作用。结果显示，相对于流产漏诊患者和正常绒毛标本的绒毛标本，RSA患者绒毛标本中MALAT1的表达显着降低。MALAT1 通过负调节 CRY2 蛋白表达促进滋养层细胞迁移和侵袭。MALAT1 招募 FBXW7 来削弱 CRY2 蛋白的稳定性。总之，滋养层细胞中 MALAT1 的下调可能与流产有关。MALAT1 可能会招募 E3 泛素连接酶 FBXW7 来诱导 CRY2 泛素介导的降解并参与滋养层迁移和侵袭。总之，滋养层细胞中 MALAT1 的下调可能与流产有关。MALAT1 可能会招募 E3 泛素连接酶 FBXW7 来诱导 CRY2 泛素介导的降解并参与滋养层迁移和侵袭。总之，滋养层细胞中 MALAT1 的下调可能与流产有关。MALAT1 可能会招募 E3 泛素连接酶 FBXW7 来诱导 CRY2 泛素介导的降解并参与滋养层迁移和侵袭。