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缺少G-补丁基序的PinX1抑制结肠直肠癌SW480细胞的增殖,诱导衰老,但不抑制端粒酶活性。

PinX1 without the G-patch motif suppresses proliferation, induces senescence, but does not inhibit telomerase activity in colorectal cancer SW480 cells.

作者信息

Zhang Rui, Zhao Jian, Wang Xu, Wang Li-Li, Xu Jian, Song Chun

机构信息

Department of Colorectal Surgery, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.

出版信息

Oncol Rep. 2014 Jul;32(1):286-92. doi: 10.3892/or.2014.3199. Epub 2014 May 20.

DOI:10.3892/or.2014.3199
PMID:24839934
Abstract

Evidence suggests that Pin2/TRF1-interacting protein X1 (PinX1) inhibits telomerase activity in many types of cancer cells. G-patch is a motif in the PinX1 protein; however, the function of G-patch in colorectal cancer cells has not been definitively elucidated. The present study investigated the antitumor activities of different PinX1 fragments in vitro, and explored the molecular mechanisms responsible for these effects. SW480 cells were transfected with pEGFP-A1-PinX1 1-328 (intact) or pEGFP-A1-PinX1 69-328 (truncated). Flow cytometry was used to observe apoptosis and the cell cycle of SW480 cells transfected with intact PinX1 or truncated PinX1. The apoptosis-related proteins, caspase 3, 8 and 9, were detected by western blotting. Our results indicate that both intact and truncated PinX1 induced apoptosis, G1 arrest, and cellular senescence. However, truncated PinX1 showed no effects on telomerase activity. Why PinX1 without G-patch has similar antitumor activities as intact PinX1 remains unclear. The mechanisms of G-patch require elucidation in subsequent studies. Finally, we detected the protein and mRNA levels of PinX1 and caspase 3, 8 and 9 in colorectal cancer specimens and confirmed that levels of PinX1 and caspase 3, 8 and 9 expression were closely linked to the poor prognosis of colorectal cancer.

摘要

有证据表明,Pin2/TRF1相互作用蛋白X1(PinX1)在多种癌细胞中抑制端粒酶活性。G-结构域是PinX1蛋白中的一个基序;然而,G-结构域在结肠癌细胞中的功能尚未得到明确阐明。本研究在体外研究了不同PinX1片段的抗肿瘤活性,并探讨了产生这些效应的分子机制。用pEGFP-A1-PinX1 1-328(完整)或pEGFP-A1-PinX1 69-328(截短)转染SW480细胞。采用流式细胞术观察转染完整PinX1或截短PinX1的SW480细胞的凋亡和细胞周期。通过蛋白质印迹法检测凋亡相关蛋白caspase 3、8和9。我们的结果表明,完整和截短的PinX1均诱导凋亡、G1期阻滞和细胞衰老。然而,截短的PinX1对端粒酶活性没有影响。为何不含G-结构域的PinX1与完整PinX1具有相似的抗肿瘤活性仍不清楚。G-结构域的机制需要在后续研究中阐明。最后,我们检测了结肠癌标本中PinX1和caspase 3、8和9的蛋白质和mRNA水平,并证实PinX1和caspase 3、8和9的表达水平与结肠癌的不良预后密切相关。

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引用本文的文献

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PINX1 promotes malignant transformation of thyroid cancer through the activation of the AKT/MAPK/β-catenin signaling pathway.PINX1通过激活AKT/MAPK/β-连环蛋白信号通路促进甲状腺癌的恶性转化。
Am J Cancer Res. 2021 Nov 15;11(11):5485-5495. eCollection 2021.
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PinX1: structure, regulation and its functions in cancer.PinX1:结构、调控及其在癌症中的功能
Oncotarget. 2016 Oct 4;7(40):66267-66275. doi: 10.18632/oncotarget.11411.
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PinX1 suppresses tumorigenesis by negatively regulating telomerase/telomeres in colorectal carcinoma cells and is a promising molecular marker for patient prognosis.PinX1通过负向调节结肠癌细胞中的端粒酶/端粒来抑制肿瘤发生,是一种很有前景的患者预后分子标志物。
Onco Targets Ther. 2016 Aug 3;9:4821-31. doi: 10.2147/OTT.S103141. eCollection 2016.
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PinX1 is up-regulated and associated with poor patients' survival in gliomas.PinX1在胶质瘤中表达上调,并与患者的不良预后相关。
Int J Clin Exp Pathol. 2015 Jun 1;8(6):6952-9. eCollection 2015.
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PinX1 inhibits cell proliferation, migration and invasion in glioma cells.PinX1抑制胶质瘤细胞的增殖、迁移和侵袭。
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