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PP4R1 interacts with HMGA2 to promote non-small-cell lung cancer migration and metastasis via activating MAPK/ERK-induced epithelial-mesenchymal transition.
Molecular Carcinogenesis ( IF 3.0 ) Pub Date : 2020-02-19 , DOI: 10.1002/mc.23168
Bin Wang 1 , Lin-Yue Pan 2 , Ning Kang 1 , Xiao-Yong Shen 1
Affiliation  

Protein phosphatase 4 regulatory subunit 1 (PP4R1) has been shown to play a role in the regulation of centrosome maturation, apoptosis, DNA repair, and tumor necrosis factor signaling. However, the function of PP4R1 in non-small-cell lung cancer remains unclear. In this study, we identify PP4R1 as an oncogene through Oncomine database mining and immunohistochemical staining, and we showed that PP4R1 is upregulated in lung cancer tissues as compared with that in normal lung tissues and correlated with a poor prognosis in lung cancer patients. Furthermore, in vitro study by wound-healing and Transwell assay showed that PP4R1 could promote migration and invasion of lung cancer cells. Mechanistic investigations revealed that PP4R1 could cooperate with high mobility group AT-hook 2 and thereby promotes epithelial-mesenchymal transition via MAPK/extracellular receptor kinase activation. Taken together, our study provides a rich resource for understanding PP4R1 in lung cancer and indicates that PP4R1 may serve as a potential biomarker in lung cancer therapies.

中文翻译:

PP4R1与HMGA2相互作用,通过激活MAPK / ERK诱导的上皮-间质转化促进非小细胞肺癌的迁移和转移。

已证明蛋白磷酸酶4调节亚基1(PP4R1)在调节中心体成熟,凋亡,DNA修复和肿瘤坏死因子信号传导中发挥作用。但是,PP4R1在非小细胞肺癌中的功能仍不清楚。在这项研究中,我们通过Oncomine数据库挖掘和免疫组织化学染色将PP4R1鉴定为致癌基因,并且我们发现与正常肺组织相比PP4R1在肺癌组织中上调,并且与肺癌患者的不良预后相关。此外,通过伤口愈合和Transwell分析的体外研究表明,PP4R1可以促进肺癌细胞的迁移和侵袭。机理研究表明,PP4R1可以与高迁移率的AT-钩2分子协同作用,从而通过MAPK /细胞外受体激酶激活促进上皮-间质转化。综上所述,我们的研究为理解PP4R1在肺癌中提供了丰富的资源,并表明PP4R1可能作为肺癌治疗中的潜在生物标志物。
更新日期:2020-04-13
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