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PELP1 在肺腺癌中的过表达促进了肿瘤细胞的 E 诱导增殖、迁移和侵袭,并预测了患者的预后更差。

Overexpression of PELP1 in Lung Adenocarcinoma Promoted E Induced Proliferation, Migration and Invasion of the Tumor Cells and Predicted a Worse Outcome of the Patients.

机构信息

Department of Pathology, Harbin Medical University-Daqing, Daqing, China.

Traditional Psychological Unit, The Third Hospital of Daqing, Daqing, China.

出版信息

Pathol Oncol Res. 2021 Apr 2;27:582443. doi: 10.3389/pore.2021.582443. eCollection 2021.

DOI:10.3389/pore.2021.582443
PMID:34257530
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8262236/
Abstract

The expression of Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) has been reported to be dysregulated in non-small cell lung carcinoma, especially in lung adenocarcinoma (LUAD). Therefore, we aimed to investigate the functional and prognostic roles of PELP1 in LUAD in this study. We first immunolocalized PELP1 in 76 cases of LUAD and 17 non-pathological or tumorous lung (NTL) tissue specimens and correlated the findings with the clinicopathological parameters of the patients. We then performed analysis including MTT, flow cytometry, wound healing, and transwell assays in order to further explore the biological roles of PELP1 in 17-β-estradiol (E) induced cell proliferation, migration, and invasion of LUAD cells. We subsequently evaluated the prognostic significance of PELP1 in LUAD patients using the online survival analysis tool Kaplan-Meier Plotter. The status of PELP1 immunoreactivity in LUAD was significantly higher than that in the NTL tissues and significantly positively correlated with less differentiated features of carcinoma cells, positive lymph node metastasis, higher clinical stage as well as the status of ERα, ERβ, and PCNA. study did reveal that E promoted cell proliferation and migration and elevated PELP1 protein level in PELP1-high A549 and H1975 cells but not in PELP1-low H-1299 cells. Knock down of PELP1 significantly attenuated E induced cell proliferation, colony formation, cell cycle progress as well as migration and invasion of A549 and H1975 cells. Kaplan-Meier Plotter revealed that LUAD cases harboring higher PELP1 expression had significantly shorter overall survival. In summary, PELP1 played a pivotal role in the estrogen-induced aggressive transformation of LUAD and could represent adverse clinical outcome of the LUAD patients.

摘要

脯氨酸、谷氨酸和亮氨酸丰富蛋白 1(PELP1)的表达已被报道在非小细胞肺癌中失调,特别是在肺腺癌(LUAD)中。因此,我们旨在研究 PELP1 在 LUAD 中的功能和预后作用。我们首先在 76 例 LUAD 和 17 例非病变或肿瘤性肺(NTL)组织标本中免疫定位 PELP1,并将结果与患者的临床病理参数相关联。然后,我们进行了包括 MTT、流式细胞术、划痕愈合和 Transwell 测定在内的分析,以进一步探索 PELP1 在 17-β-雌二醇(E)诱导的 LUAD 细胞增殖、迁移和侵袭中的生物学作用。随后,我们使用在线生存分析工具 Kaplan-Meier Plotter 评估了 PELP1 在 LUAD 患者中的预后意义。PELP1 免疫反应性在 LUAD 中的状态明显高于 NTL 组织,并且与癌细胞分化程度较低、淋巴结转移阳性、临床分期较高以及 ERα、ERβ 和 PCNA 的状态呈显著正相关。研究确实表明,E 促进了 PELP1 高表达的 A549 和 H1975 细胞的增殖和迁移,并提高了 PELP1 蛋白水平,但在 PELP1 低表达的 H-1299 细胞中则没有。PELP1 的敲低显著减弱了 E 诱导的 A549 和 H1975 细胞的增殖、集落形成、细胞周期进展以及迁移和侵袭。Kaplan-Meier Plotter 显示,携带更高 PELP1 表达的 LUAD 病例的总生存期明显缩短。总之,PELP1 在雌激素诱导的 LUAD 侵袭性转化中发挥了关键作用,可能代表 LUAD 患者不良的临床结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea09/8262236/ced754503095/pore-27-582443-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea09/8262236/ced754503095/pore-27-582443-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea09/8262236/0db29a93bc7c/pore-27-582443-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea09/8262236/ae466fbbc88d/pore-27-582443-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea09/8262236/2d83c44f5399/pore-27-582443-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea09/8262236/12ef3b691dc8/pore-27-582443-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea09/8262236/ced754503095/pore-27-582443-g005.jpg

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