Abstract
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.
Highlights
The Polycomb group (PcG) is an important family of transcriptional regulators that controls growth and tumorigenesis
The expression of Polycomb-like 2 (PCL2) appeared to be different among the 33 tumor types, with lower than normal expressions in adrenocortical carcinoma (ACC), kidney Chromophobe (KICH), LAML, lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), ovarian serous cystadenocarcinoma (OV), prostate adenocarcinoma (PRAD) and Thyroid carcinoma (THCA), and higher than normal expressions in diffuse large B-cell lymphoma (DLBC), esophageal cancer (ESCA), and head and neck squamous cell carcinoma (HNSC) (Fig. 1a)
We demonstrated that in U87 cells, deazaneplanocin A (DZNeP) reduced the increases in the EZH2 protein level caused by high expression PCL2transfected cells (hPCL2) expressions and the protein expression of SUZ12 and EED in Polycomb Repressive Complex 2 (PRC2) were reduced compared to that in the control (Fig. 6c)
Summary
The Polycomb group (PcG) is an important family of transcriptional regulators that controls growth and tumorigenesis. We found that the PCL2 gene promoted tumor cell proliferation, enhanced the colony formation ability, and increased S phase in the cell cycle. Polycomb group (PcG) proteins are conserved epigenetic transcriptional repressors that control numerous developmental gene expressions and have recently been implicated in the modulation of embryonic stem cell (ESC) fate [1]. Cases of GBM with H3F3AK27 mutations show high frequency of TP53 mutations, hypomethylation of DNA, midline location and spread of diffuse pontine glioma, and poor prognosis Mutations in these genes are closely related to the alternate expansions of specific gene expression profiles, leading to the formation of gliomas [11]. We hypothesized that PCL2 might promote the growth of cells in gliomas by altering the effect of PRC2 on histone methylation modifications. We detected PRC2-related protein levels and histone methylation
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