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PURα mediates epithelial-mesenchymal transition to promote esophageal squamous cell carcinoma progression by regulating Snail2
Cancer Letters ( IF 9.7 ) Pub Date : 2020-11-02 , DOI: 10.1016/j.canlet.2020.10.030
Jiajia Gao , Lusong Tian , Yulin Sun , Wei Li , Lina Zhao , Yan Sun , Zongpan Jing , Lanping Zhou , Fang Liu , Xiaohang Zhao

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.



中文翻译:

PURα通过调节Snail2介导上皮-间质转化,促进食管鳞状细胞癌进展

食道鳞状细胞癌(ESCC)是世界上最常见的致死性癌症之一。据报道,富含嘌呤的元素结合蛋白α(PURα)的失调与多种癌症的进展有关,而这种失调可导致PURA综合征的发生,但其功能和ESCC进展的潜在机制尚不清楚。在这里,我们首先证明了PURα在体外体内均可促进ESCC细胞的生长,迁移和侵袭。然后对225个ESCC组织进行了免疫组织化学分析,结果表明高PURα表达与淋巴结转移和AJCC分期成正相关,而PURα表达阳性的ESCC患者生存率较差。另外,RNA测序表明PURα诱导了ESCC中的上皮-间质转化(EMT),这通过qPCR,蛋白质印迹和免疫荧光分析得到了进一步证实。从机制上讲,PURα通过结合Snail2启动子区域来增强Snail2的转录。击倒Snail2可逆转PURα诱导的EMT,并抑制ESCC细胞的迁移和侵袭。总之,这项研究表明,PURα促进ESCC进程中Snail2转录活性诱导EMT。

更新日期:2020-12-16
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