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PURα 通过调节 Snail2 介导上皮-间充质转化促进食管鳞癌进展。

PURα mediates epithelial-mesenchymal transition to promote esophageal squamous cell carcinoma progression by regulating Snail2.

机构信息

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

出版信息

Cancer Lett. 2021 Feb 1;498:98-110. doi: 10.1016/j.canlet.2020.10.030. Epub 2020 Nov 2.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal cancers in the world. Dysregulation of purine-rich element binding protein alpha (PURα), which contributes to the initiation of PURΑ syndrome, is reportedly involved in the progression of multiple cancers, but its function and underlying mechanisms in ESCC progression remain unclear. Here, we first demonstrated that PURα promoted cell growth, migration and invasion in ESCC both in vitro and in vivo. An immunohistochemistry assay was then performed on 225 ESCC tissues, showing that high PURα expression was positively associated with lymph node metastasis and the AJCC stage, and the ESCC patients with positive PURα expression had worse survival. In addition, RNA sequencing implied that PURα induced epithelial-mesenchymal transition (EMT) in ESCC, which was further confirmed by qPCR, Western blotting and immunofluorescence analyses. Mechanistically, PURα enhanced the transcription of Snail2 by binding to its promoter region. Knockdown of Snail2 reversed PURα-induced EMT and inhibited the migration and invasion of ESCC cells. In conclusion, this study indicated that PURα promotes Snail2 transcriptional activity to induce EMT during ESCC progression.

摘要

食管鳞状细胞癌 (ESCC) 是世界上最常见的致命癌症之一。富含嘌呤元件结合蛋白α (PURα) 的失调,据称参与了多种癌症的进展,但它在 ESCC 进展中的功能和潜在机制仍不清楚。在这里,我们首次证明 PURα 在体外和体内均促进 ESCC 中的细胞生长、迁移和侵袭。然后对 225 例 ESCC 组织进行免疫组织化学检测,结果表明 PURα 高表达与淋巴结转移和 AJCC 分期呈正相关,且 PURα 表达阳性的 ESCC 患者生存状况较差。此外,RNA 测序表明 PURα 在 ESCC 中诱导上皮-间充质转化 (EMT),这通过 qPCR、Western blot 和免疫荧光分析进一步得到证实。在机制上,PURα 通过结合其启动子区域增强了 Snail2 的转录。Snail2 的敲低逆转了 PURα 诱导的 EMT,并抑制了 ESCC 细胞的迁移和侵袭。综上所述,本研究表明 PURα 通过诱导 EMT 促进 Snail2 的转录活性,从而促进 ESCC 的进展。

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