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通过p-P38介导的GPX4/xCT下调，PTPN18沉默诱导子宫内膜癌细胞发生铁死亡。

Silencing of PTPN18 Induced Ferroptosis in Endometrial Cancer Cells Through p-P38-Mediated GPX4/xCT Down-Regulation.

作者信息

Wang Haibo, Peng Siyuan, Cai Junhong, Bao Shan

机构信息

Department of Gynaecology and Obstetrics, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, People's Republic of China.

Key Laboratory of Cell and Molecular Genetic Translational Medicine in Hainan Province, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, People's Republic of China.

出版信息

Cancer Manag Res. 2021 Feb 19;13:1757-1765. doi: 10.2147/CMAR.S278728. eCollection 2021.

DOI:10.2147/CMAR.S278728
PMID:33642877
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7903946/
Abstract

BACKGROUND

Endometrial cancer (EC) is the fourth most common neoplasm and the eighth leading cause of cancer death in females worldwide. PTPN18 is a member of the protein tyrosine phosphatases (PTP) family, which is associated with the occurrence and progression of various human cancers. PTPN18 was up-regulated in endometrial cancer tissues and high level of PTPN18 promoted proliferation and metastasis of EC cells.

METHODS

The expression of PTPN18, GPX4 and xCT in endometrial cancer tissues and KLE cells was detected by immunohistochemistry and Western blot, respectively. Lentiviral transfection were used to silence PTPN18 level in KLE cells. The Ros level in KLE cells was examined by ELISA assay.

RESULTS

In the present study, we found that silencing of PTPN18 induced ferroptosis in KLE endometrial cancer cells. PTPN18 knockdown increased intracellular ROS level and down-regulated GPX4 and xCT expression. Besides, silencing of PTPN18 also induced the expression of p-p38.

CONCLUSION

We concluded that silencing of PTPN18 might induce ferroptosis by targeting the p-p38/GPX4/xCT axis. The results provide critical insight into the application of PTPN18 knockdown in EC intervention.

摘要

背景

子宫内膜癌（EC）是全球女性中第四常见的肿瘤，也是癌症死亡的第八大主要原因。PTPN18是蛋白酪氨酸磷酸酶（PTP）家族的成员，与多种人类癌症的发生和发展有关。PTPN18在子宫内膜癌组织中上调，高水平的PTPN18促进了EC细胞的增殖和转移。

方法

分别通过免疫组织化学和蛋白质印迹法检测子宫内膜癌组织和KLE细胞中PTPN18、GPX4和xCT的表达。采用慢病毒转染法沉默KLE细胞中的PTPN18水平。通过ELISA法检测KLE细胞中的ROS水平。

结果

在本研究中，我们发现沉默PTPN18可诱导KLE子宫内膜癌细胞发生铁死亡。敲低PTPN18可增加细胞内ROS水平，并下调GPX4和xCT的表达。此外，沉默PTPN18还可诱导p-p38的表达。

结论

我们得出结论，沉默PTPN18可能通过靶向p-p38/GPX4/xCT轴诱导铁死亡。这些结果为敲低PTPN18在EC干预中的应用提供了关键见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d8/7903946/72b2eb8ba065/CMAR-13-1757-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d8/7903946/9f6fb4357c72/CMAR-13-1757-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d8/7903946/bb7305428e1b/CMAR-13-1757-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d8/7903946/3338cddef8a8/CMAR-13-1757-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d8/7903946/fb70e9460b60/CMAR-13-1757-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d8/7903946/72b2eb8ba065/CMAR-13-1757-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d8/7903946/9f6fb4357c72/CMAR-13-1757-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d8/7903946/bb7305428e1b/CMAR-13-1757-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d8/7903946/3338cddef8a8/CMAR-13-1757-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d8/7903946/fb70e9460b60/CMAR-13-1757-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d8/7903946/72b2eb8ba065/CMAR-13-1757-g0005.jpg

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