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CCAAT 增强子结合蛋白α通过抑制 Wnt/β-连环蛋白信号通路抑制卵巢癌细胞的增殖、转移和上皮间质转化。

CCAAT enhancer binding protein α suppresses proliferation, metastasis, and epithelial-mesenchymal transition of ovarian cancer cells via suppressing the Wnt/β-catenin signaling.

机构信息

Department of Gynecology and Obstetrics, Affiliated Hospital of Bei Hua University, Jilin, Jilin, China.

出版信息

Neoplasma. 2021 May;68(3):602-612. doi: 10.4149/neo_2021_210103N2. Epub 2021 Mar 30.

DOI:10.4149/neo_2021_210103N2
PMID:33780265
Abstract

CCAAT enhancer-binding protein alpha (CEBPA, also known as C/EBPα) is a transcription factor that plays an essential role in regulating terminal differentiation and cell proliferation of many tissues. The objective of this study was to explore the potential function of CEBPA in ovarian cancer. The expression of CEBPA in ovarian cancer samples and adjacent normal tissues was evaluated by qRT-PCR. The putative role of CEBPA in ovarian cancer cells was evaluated by immunohistochemistry, western blot, cell viability assay, BrdU incorporation assay, soft agar colony formation assay, Transwell cell migration and invasion assay, tumor xenograft formation, and lung metastasis model. We found that CEBPA was downregulated in ovarian cancer samples and predicted a poor prognosis. CRISPR/Cas9-mediated CEBPA knockout promoted proliferation, anchorage-independent growth, migration, invasion, and EMT of ovarian cancer cells, while enforced CEPBA expression suppressed proliferation, anchorage-independent growth, migration, invasion, EMT, tumor xenograft growth, and lung metastasis of ovarian cancer cells. Furthermore, we found that the knockout of CEBPA activated Wnt/β-catenin signaling in ovarian cancer cells, while CEBPA overexpression suppressed Wnt/β-catenin activation. Our data indicated that CEBPA acted as a tumor suppressor in ovarian cancer, and might be a potential prognostic marker for ovarian cancer treatment.

摘要

CCAAT 增强子结合蛋白α(CEBPA,也称为 C/EBPα)是一种转录因子,在调节许多组织的终末分化和细胞增殖中起着至关重要的作用。本研究旨在探讨 CEBPA 在卵巢癌中的潜在功能。通过 qRT-PCR 评估 CEBPA 在卵巢癌样本和相邻正常组织中的表达。通过免疫组织化学、Western blot、细胞活力测定、BrdU 掺入测定、软琼脂集落形成测定、Transwell 细胞迁移和侵袭测定、肿瘤异种移植形成和肺转移模型评估 CEBPA 在卵巢癌细胞中的潜在作用。我们发现 CEBPA 在卵巢癌样本中下调,预测预后不良。CRISPR/Cas9 介导的 CEBPA 敲除促进了卵巢癌细胞的增殖、非锚定依赖性生长、迁移、侵袭和 EMT,而强制表达 CEPBA 则抑制了卵巢癌细胞的增殖、非锚定依赖性生长、迁移、侵袭、EMT、肿瘤异种移植生长和肺转移。此外,我们发现 CEBPA 敲除激活了卵巢癌细胞中的 Wnt/β-catenin 信号通路,而 CEBPA 过表达抑制了 Wnt/β-catenin 的激活。我们的数据表明,CEBPA 在卵巢癌中起肿瘤抑制作用,可能是卵巢癌治疗的潜在预后标志物。

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