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Paip1 通过 AKT/GSK-3β 通路预测肺腺癌不良预后并促进肿瘤进展。

Paip1 predicts poor prognosis and promotes tumor progression through AKT/GSK-3β pathway in lung adenocarcinoma.

机构信息

Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji 133002, China; Key Laboratory of the Science and Technology Department of Jilin Province, Yanji 133002, China.

Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji 133002, China; Key Laboratory of the Science and Technology Department of Jilin Province, Yanji 133002, China.

出版信息

Hum Pathol. 2019 Apr;86:233-242. doi: 10.1016/j.humpath.2018.11.017. Epub 2018 Nov 26.

DOI:10.1016/j.humpath.2018.11.017
PMID:30496797
Abstract

The expression and biological function of Paip1 remain poorly understood in most human cancers. The objective of this research is to investigate its clinical significance and roles in lung adenocarcinoma (LADC). Immunohistochemistry was used to determine Paip1 expression in 58 cases of LADC patients with strict follow-up and 60 cases of adjacent normal lung tissues. Paip1 protein was upregulated in 77.6% (45/58) LADC tissues compared with adjacent normal lung tissues. The overexpression of Paip1 was significantly correlated with histologic grade, clinical stage, and poor prognosis. Small interfering RNA-mediated transfection was performed in A549 and H1299 cells. Paip1 depletion attenuated the proliferation and migration of A549 and H1299 cells. Paip1 also changed the expression of epithelial-to-mesenchymal transition markers including E-cadherin, Vimentin, Slug, and Snail. Furthermore, Paip1 regulated AKT/GSK-3β oncogenic signaling pathways. In conclusions, Paip1 expression is frequently upregulated in LADC, and its overexpression correlates with poor prognosis in LADC patients. Attenuated Paip1 expression suppresses proliferation and epithelial-to-mesenchymal transition-related migration of A549 and H1299 cells by regulating the AKT/GSK-3β signaling pathway.

摘要

Paip1 在大多数人类癌症中的表达和生物学功能仍知之甚少。本研究旨在探讨其在肺腺癌(LADC)中的临床意义和作用。免疫组织化学法检测 58 例严格随访的 LADC 患者和 60 例相邻正常肺组织中 Paip1 的表达。与相邻正常肺组织相比,77.6%(45/58)的 LADC 组织中 Paip1 蛋白表达上调。Paip1 的过表达与组织学分级、临床分期和预后不良显著相关。在 A549 和 H1299 细胞中,采用小干扰 RNA 介导的转染。Paip1 耗竭减弱了 A549 和 H1299 细胞的增殖和迁移。Paip1 还改变了上皮间质转化标志物包括 E-钙黏蛋白、波形蛋白、Slug 和 Snail 的表达。此外,Paip1 调节 AKT/GSK-3β 致癌信号通路。总之,Paip1 在 LADC 中表达频繁上调,其过表达与 LADC 患者的不良预后相关。减弱的 Paip1 表达通过调节 AKT/GSK-3β 信号通路抑制 A549 和 H1299 细胞的增殖和上皮间质转化相关迁移。

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