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桥粒芯蛋白-2的上调与胶质瘤的进展相关。

Up-regulation of plakophilin-2 is correlated with the progression of glioma.

作者信息

Zhang Degeng, Qian Yuxia, Liu Xiaoxing, Yu Hong, Zhao Niangao, Wu Zhengdong

机构信息

Department of Oncology, Taizhou People's Hospital, Taizhou, China.

Department of Hematology, Taizhou People's Hospital, Taizhou, China.

出版信息

Neuropathology. 2017 Jun;37(3):207-216. doi: 10.1111/neup.12363. Epub 2017 Jan 26.

DOI:10.1111/neup.12363
PMID:28124385
Abstract

Glioma is the most common type of primary brain tumor in the CNS. Due to its poor prognosis and high mortality rates, it is urgent to find out more effective therapies. Plakophilin-2 (PKP2) is a widespread desmosomal plaque protein. Recently, the important roles of PKP2 in the proliferation and migration of cancer cells and tumor progression has been shown. However, the expression and potential function of PKP2 in glioma was still unclear. In this study, we demonstrated that PKP2 protein expression level was increased in glioma tissues compared with normal brain tissues, and its level was significantly associated with the Ki-67 expression and WHO grade by Western blot analysis and immunohistochemistry. Clinically, high PKP2 expression was tightly related to poor prognosis of glioma patients. Interestingly, we found that down-regulated PKP2 expression was shown to inhibit the migration of cells in glioma. Moreover, cell counting kit (CCK)-8 and colony formation analyses proved that reduced expression of PKP2 could weaken glioma cell proliferation. Taken together, these data uncover a potential role for PKP2 in the pathogenic process of glioma, suggesting that PKP2 may be a promising therapeutic target of glioma.

摘要

胶质瘤是中枢神经系统中最常见的原发性脑肿瘤类型。由于其预后较差且死亡率较高,因此迫切需要找到更有效的治疗方法。桥粒芯蛋白2(PKP2)是一种广泛存在的桥粒斑块蛋白。最近,PKP2在癌细胞增殖、迁移及肿瘤进展中的重要作用已得到证实。然而,PKP2在胶质瘤中的表达及潜在功能仍不清楚。在本研究中,我们通过蛋白质免疫印迹分析和免疫组织化学方法证明,与正常脑组织相比,胶质瘤组织中PKP2蛋白表达水平升高,且其水平与Ki-67表达及世界卫生组织(WHO)分级显著相关。临床上,PKP2高表达与胶质瘤患者的不良预后密切相关。有趣的是,我们发现下调PKP2表达可抑制胶质瘤细胞的迁移。此外,细胞计数试剂盒(CCK)-8和集落形成分析证明,PKP2表达降低会削弱胶质瘤细胞的增殖。综上所述,这些数据揭示了PKP2在胶质瘤发病过程中的潜在作用,表明PKP2可能是一种有前景的胶质瘤治疗靶点。

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Nat Commun. 2023 Aug 22;14(1):5106. doi: 10.1038/s41467-023-40596-0.
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A glycolysis-related two-gene risk model that can effectively predict the prognosis of patients with rectal cancer.一个与糖酵解相关的两基因风险模型,可有效预测直肠癌患者的预后。
Hum Genomics. 2022 Feb 2;16(1):5. doi: 10.1186/s40246-022-00377-0.
3
Long non-coding RNA HCG11 enhances osteosarcoma phenotypes by sponging miR-1245b-5p that directly inhibits plakophilin 2.
长链非编码 RNA HCG11 通过海绵吸附 miR-1245b-5p 增强骨肉瘤表型,miR-1245b-5p 可直接抑制桥粒斑蛋白 2。
Bioengineered. 2022 Jan;13(1):140-154. doi: 10.1080/21655979.2021.2010367.
4
CRISPR/Cas9 library screening uncovered methylated PKP2 as a critical driver of lung cancer radioresistance by stabilizing β-catenin.CRISPR/Cas9 文库筛选发现,甲基化 PKP2 通过稳定 β-连环蛋白成为肺癌放射抵抗的关键驱动因素。
Oncogene. 2021 Apr;40(16):2842-2857. doi: 10.1038/s41388-021-01692-x. Epub 2021 Mar 19.
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Cancer Manag Res. 2021 Jan 22;13:559-570. doi: 10.2147/CMAR.S281663. eCollection 2021.
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