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Twist-1 通过 PI3K/AKT 通路刺激葡萄胎的恶性行为。

Twist-1 Stimulates the Malignant Behaviors of Hydatidiform Mole via the PI3K/AKT Pathway.

机构信息

Department of Gynecology, Jinan Maternity and Child Care Hospital, 250001 Jinan, Shandong, China.

Department of Pathology, Jinan Maternity and Child Care Hospital, 250001 Jinan, Shandong, China.

出版信息

Discov Med. 2024 Feb;36(181):286-293. doi: 10.24976/Discov.Med.202436181.27.

DOI:10.24976/Discov.Med.202436181.27
PMID:38409834
Abstract

BACKGROUND

Hydatidiform mole (HM) is a common pregnancy disease among women of gestational age. Twist-related protein 1 (Twist-1) is involved in the development of various tumors, but its role in HM is poorly defined. This study aimed to explore Twist-1 expression and its biological function in HM cells.

METHODS

Twist-1 expression in HM was detected by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). The effects of silencing Twist-1 on choriocarcinoma (CCA) cell proliferation were detected by cell counting kit-8 (CCK-8) and clone formation assays. CCA cell migration and invasion were detected through transwell assay. Western blot was used to detect epithelial-mesenchymal transition (EMT) and the expression of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins.

RESULTS

Twist-1 expression was upregulated in HM tissues ( < 0.001) and CCA cells ( < 0.01). Twist-1 silencing inhibited proliferation of BeWo and JAR cells ( < 0.01, < 0.05) as shown by CCK-8 assay ( < 0.01) and clone formation assays ( < 0.01, < 0.05). Twist-1 silencing inhibited the migration ( < 0.01) and invasion activity ( < 0.01, < 0.05) of BeWo and JAR cells. Western blot results showed that Twist-1 silencing promoted E-cadherin ( < 0.01) expression, and inhibited N-cadherin ( < 0.01, < 0.05) and vimentin ( < 0.01, < 0.05) expression in BeWo and JAR cells. Twist-1 downregulation decreased protein levels of p-PI3K ( < 0.01) and p-AKT ( < 0.01, < 0.05) in BeWo and JAR cells.

CONCLUSIONS

Silencing Twist-1 inhibits the malignant behavior of CCA cells, which may play a part by inhibiting the EMT process and the PI3K/AKT pathway.

摘要

背景

葡萄胎(HM)是一种常见的妊娠疾病,发生于育龄妇女。 twist 相关蛋白 1(Twist-1)参与多种肿瘤的发生发展,但在 HM 中的作用尚不清楚。本研究旨在探讨 Twist-1 在 HM 细胞中的表达及其生物学功能。

方法

采用免疫组织化学和实时定量聚合酶链反应(qRT-PCR)检测 HM 中 Twist-1 的表达。通过细胞计数试剂盒-8(CCK-8)和克隆形成实验检测沉默 Twist-1 对绒毛膜癌(CCA)细胞增殖的影响。Transwell 实验检测 CCA 细胞迁移和侵袭。Western blot 检测上皮间质转化(EMT)及磷脂酰肌醇 3-激酶/蛋白激酶 B(PI3K/AKT)通路相关蛋白的表达。

结果

HM 组织( < 0.001)和 CCA 细胞( < 0.01)中 Twist-1 的表达上调。沉默 Twist-1 抑制 BeWo 和 JAR 细胞的增殖( < 0.01, < 0.05),CCK-8 实验( < 0.01)和克隆形成实验( < 0.01, < 0.05)。沉默 Twist-1 抑制 BeWo 和 JAR 细胞的迁移( < 0.01)和侵袭活性( < 0.01, < 0.05)。Western blot 结果显示,沉默 Twist-1 促进 E-钙黏蛋白( < 0.01)的表达,抑制 BeWo 和 JAR 细胞中 N-钙黏蛋白( < 0.01, < 0.05)和波形蛋白( < 0.01, < 0.05)的表达。下调 Twist-1 降低了 BeWo 和 JAR 细胞中 p-PI3K( < 0.01)和 p-AKT( < 0.01, < 0.05)的蛋白水平。

结论

沉默 Twist-1 抑制 CCA 细胞的恶性行为,可能通过抑制 EMT 过程和 PI3K/AKT 通路发挥作用。

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