Polycomb-like 2 regulates PRC2 components to affect proliferation in glioma cells
Polycomb-like 2 regulates PRC2 components to affect proliferation in glioma cells
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DOI：
10.1007/s11060-020-03538-0
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发表时间：
2020-05
影响因子：
3.9
通讯作者：
Fei Wang;Yongying Gao;Y. Lv;Yanwei Wu;Yongzheng Guo;F. Du;Shixiong Wang;Jiaxian Yu;Xiangmei Cao;P. A. Li
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文献类型：
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作者：
Fei Wang;Yongying Gao;Y. Lv;Yanwei Wu;Yongzheng Guo;F. Du;Shixiong Wang;Jiaxian Yu;Xiangmei Cao;P. A. Li
Polycomb家族（Polycomb group，PcG）是一个重要的转录调控因子家族，在肿瘤的发生和生长过程中起重要作用。PcG主要由两种复合物PRC 1和Polycomb Repressive Complex 2（PRC 2）组成。已知多梳样蛋白2（PCL 2）与PRC 2蛋白相互作用。PCL 2在胶质瘤发生发展中的作用尚不清楚。方法我们利用肿瘤基因组图谱（TCGA）数据库检测PCL 2在各种肿瘤中的表达。收集117例临床胶质瘤（WHOI-IV），采用免疫组化法检测PCL 2的表达及定位。用过表达和干扰的PCL 2感染胶质瘤细胞U87/U251。采用CCK-8法、集落形成实验、EdU法、细胞周期和凋亡检测细胞增殖和凋亡。Western blot检测PRC 2相关核心蛋白的表达。DZNeP干预后，PRC 2蛋白表达再次测量，以讨论PCL 2的作用机制。结果TCGA数据库结果和免疫组化染色结果表明，PCL 2在胶质瘤中高表达。我们发现，PCL 2基因促进肿瘤细胞增殖，增强殖民地形成能力，并增加细胞周期中的S期。PCL 2的过表达上调EZH 2和EED（PRC 2的两个核心成员）的表达水平，降低SUZ 12的表达，增加H3 K27三甲基化（H3 K27 me 3）、H3 K4二甲基化（H3 K4 me 2）的水平，并降低H3 K9二甲基化（H3 K9 me 2）。结论PCL 2作为PRC 2的重要辅助蛋白，不仅可以改变PRC 2各组分的表达，而且可以影响组蛋白甲基化水平。因此，PCL 2可能是调节PRC 2成员之间协同作用的重要枢纽。本研究揭示了PCL 2作为肿瘤研究的一个新靶点，为今后胶质瘤的研究开辟了一条新的途径。
IntroductionThe Polycomb group (PcG) is an important family of transcriptional regulators that controls growth and tumorigenesis. The PcG mainly consists of two complexes, PRC1 and Polycomb Repressive Complex 2 (PRC2). Polycomb-like 2 (PCL2) is known to interact with the PRC2 protein. The role of PCL2 in the development and progression of glioma is unclear.MethodsWe use The Cancer Genome Atlas (TCGA) database to detect the expression of PCL2 in various tumors. 117 cases of clinical glioma (WHOI–IV) were collected, and PCL2 expression and localization were detected by immunohistochemical staining. Glioma cells U87/U251 were infected with overexpressed and interfered PCL2. CCK8 assay, colony formation assay, EdU method, cell cycle and apoptosis were used to detect cell proliferation and apoptosis. Western blot was used to detect the expression of PRC2-related core proteins. After DZNeP intervention, PRC2 protein expression was again measured to discuss the mechanism of PCL2 action.ResultsTCGA database results and immunohistochemical staining results suggest that PCL2 is highly expressed in gliomas. We found that the PCL2 gene promoted tumor cell proliferation, enhanced the colony formation ability, and increased S phase in the cell cycle. The overexpression of PCL2 upregulated the expression levels of EZH2 and EED (two core members of PRC2), decreased the expression of SUZ12, increased the level of H3K27 trimethylation (H3K27me3), H3K4 dimethylation (H3K4me2), and decreased H3K9 dimethylation (H3K9me2). The result after interfering with PCL2 was the opposite.ConclusionsAs an important accessory protein of PRC2, PCL2 can not only change the expression of PRC2 components, but also affect the expression level of Histone methylation. Therefore, PCL2 may be an important hub for regulating the synergy among PRC2 members. This study revealed PCL2 as a new target for tumor research and open up a new avenue for future research in glioma.