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TIPE1 通过促进半胱天冬酶依赖性凋亡来抑制卵巢肿瘤生长。

TIPE1 impairs ovarian tumor growth by promoting caspase-dependent apoptosis.

作者信息

Li Tingting, Jia Lei, Deng Yu, Wang Bo, Quan Song

机构信息

Department of Gynecology and Obstetrics, Center for Reproductive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Reproductive Medicine Research Center, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510655, P.R. China.

出版信息

Oncol Lett. 2020 Dec;20(6):365. doi: 10.3892/ol.2020.12227. Epub 2020 Oct 15.

DOI:10.3892/ol.2020.12227
PMID:33133265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7590423/
Abstract

Tumor necrosis factor-α-induced protein 8-like 1 (TIPE1) functions as a tumor suppressor in several types of cancer, including lung and breast cancer. The present study aimed to determine the level of expression and the function of TIPE1 in ovarian cancer. TIPE1 expression was determined in tissue microarrays and ovarian cancer cells, and these data were analyzed to assess the association between TIPE1 expression and prognosis in patients with ovarian cancer. The potential antitumor effects of TIPE1 were investigated and in a xenograft mouse model. Furthermore, the underlying molecular mechanism by which TIPE1 regulates ovarian cancer growth was determined via flow cytometric analysis, western blotting and rescue experiments. The results of the present study indicated that TIPE1 levels were markedly decreased in ovarian cancer tissues, and its level of expression was associated with a favorable prognosis of patients with ovarian cancer. In addition, ectopic TIPE1 expression significantly impaired A2780 and SKOV3 cell proliferation and colony formation , which was accompanied by efficient inhibition of xenograft tumor growth in mice. Investigations into the underlying molecular mechanism demonstrated that TIPE1 induced ovarian cancer cell apoptosis by promoting caspase protein expression. Inhibition of caspase-dependent apoptosis by z-VAD blocked TIPE1-mediated inhibition of the proliferation and induction of apoptosis in ovarian cancer cells. Collectively, the results of the present study suggest that TIPE1 may be a potential prognostic predictor and therapeutic target for patients with ovarian cancer.

摘要

肿瘤坏死因子-α诱导蛋白8样1（TIPE1）在包括肺癌和乳腺癌在内的多种癌症中发挥肿瘤抑制作用。本研究旨在确定TIPE1在卵巢癌中的表达水平及其功能。在组织芯片和卵巢癌细胞中检测了TIPE1的表达，并对这些数据进行分析，以评估TIPE1表达与卵巢癌患者预后之间的关联。在异种移植小鼠模型中研究了TIPE1的潜在抗肿瘤作用。此外，通过流式细胞术分析、蛋白质印迹和拯救实验确定了TIPE1调节卵巢癌生长的潜在分子机制。本研究结果表明，TIPE1水平在卵巢癌组织中显著降低，其表达水平与卵巢癌患者的良好预后相关。此外，异位表达TIPE1显著损害A2780和SKOV3细胞的增殖和集落形成，同时有效抑制小鼠异种移植瘤的生长。对潜在分子机制的研究表明，TIPE1通过促进半胱天冬酶蛋白表达诱导卵巢癌细胞凋亡。z-VAD抑制半胱天冬酶依赖性凋亡可阻断TIPE1介导的对卵巢癌细胞增殖的抑制和凋亡的诱导。总的来说，本研究结果表明，TIPE1可能是卵巢癌患者潜在的预后预测指标和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2644/7590423/38574d2a125b/ol-20-06-12227-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2644/7590423/cdf470cb7753/ol-20-06-12227-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2644/7590423/64c478c40c31/ol-20-06-12227-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2644/7590423/8d260d98bed3/ol-20-06-12227-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2644/7590423/aabdfe80944c/ol-20-06-12227-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2644/7590423/38574d2a125b/ol-20-06-12227-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2644/7590423/cdf470cb7753/ol-20-06-12227-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2644/7590423/64c478c40c31/ol-20-06-12227-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2644/7590423/8d260d98bed3/ol-20-06-12227-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2644/7590423/aabdfe80944c/ol-20-06-12227-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2644/7590423/38574d2a125b/ol-20-06-12227-g04.jpg

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引用本文的文献

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J Oncol. 2021 Jun 3;2021:5538911. doi: 10.1155/2021/5538911. eCollection 2021.

本文引用的文献

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Cancer statistics, 2020.癌症统计数据，2020 年。
CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.
2
KRT17 as a prognostic biomarker for stage II colorectal cancer.KRT17 作为 II 期结直肠癌的预后生物标志物。
Carcinogenesis. 2020 Jul 10;41(5):591-599. doi: 10.1093/carcin/bgz192.
3
TIPE1 Inhibits Breast Cancer Proliferation by Downregulating ERK Phosphorylation and Predicts a Favorable Prognosis.TIPE1通过下调ERK磷酸化抑制乳腺癌增殖并预示良好预后。
Front Oncol. 2019 May 22;9:400. doi: 10.3389/fonc.2019.00400. eCollection 2019.
4
TIPE1 impairs stemness maintenance in colorectal cancer through directly targeting β-catenin.TIPE1 通过直接靶向β-catenin 来损害结直肠癌细胞的干性维持。
Carcinogenesis. 2020 Mar 13;41(1):25-35. doi: 10.1093/carcin/bgz079.
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Epithelial ovarian cancer: Evolution of management in the era of precision medicine.上皮性卵巢癌：精准医学时代的治疗进展。
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TIPE2 Suppresses Pseudomonas aeruginosa Keratitis by Inhibiting NF-κB Signaling and the Infiltration of Inflammatory Cells.TIPE2 通过抑制 NF-κB 信号通路和炎症细胞浸润抑制铜绿假单胞菌角膜炎。
J Infect Dis. 2019 Aug 9;220(6):1008-1018. doi: 10.1093/infdis/jiz246.
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Effect of TIPE1 on Immune Function of Dendritic Cells and Its Signaling Pathway in Septic Mice.TIPE1 对脓毒症小鼠树突状细胞免疫功能及其信号通路的影响。
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p62 aggregates mediated Caspase 8 activation is responsible for progression of ovarian cancer.p62 聚集物介导的 Caspase 8 激活负责卵巢癌的进展。
J Cell Mol Med. 2019 Jun;23(6):4030-4042. doi: 10.1111/jcmm.14288. Epub 2019 Apr 2.
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