Polycomb-like 2 regulates PRC2 components to affect proliferation in glioma cells

Abstract

Introduction The 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. Methods We 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. Results TCGA 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. Conclusions As 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.

Tissue-Specific Tumour Suppressor and Oncogenic Activities of the Polycomb-like Protein MTF2

“…MTF2 has also been associated with the development and progression of glioblastoma, an aggressive brain tumour [102]. In this study, immunohistochemistry results from human glioma samples corroborated the results from the TCGA data analysis showing elevated MTF2 expression in glioblastoma multiforme (GBM) and lower-grade glioma.…”

“…Of note, overexpression of MTF2 led to the enhanced expressions of the core component proteins of PRC2, such as EZH2 and EED, with a concomitant decrease in SUZ12. This observation indicates the multidimensional role of MTF2, such that it not only mediates PRC2 gene targeting, but it may also impact expression/stability of the core subunits [102]. Additionally, inhibition of EZH2 by small molecules nullified the cell growth-promoting property of MTF2, consistent with the oncogenic effects of MTF2 being PRC2-dependent.…”

“…In this study, immunohistochemistry results from human glioma samples corroborated the results from the TCGA data analysis showing elevated MTF2 expression in glioblastoma multiforme (GBM) and lower-grade glioma. To test the role of MTF2 functionally, Wang et al [102] overexpressed MTF2 in the human glioblastoma cell line U87 with adenoviral vector. U87 cells overexpressing MTF2 displayed higher proliferation.…”

Critical Roles of Polycomb Repressive Complexes in Transcription and Cancer

“…However, the upregulation of EED and SUZ12 is often accompanied by the upregulation of EZH2, exerting oncogenic effects mainly through PRC2-mediated gene silencing [ 200 , 201 ]. In addition, the oncogenic roles played by other subunits of PRC2, such as PCL1/2/3 and EPOP have also been linked to their regulation of PRC2 activity or promotion of PRC2 recruitment to chromatin ( Table 2 ) [ 75 , 215 , 219 , 222 ]. In contrast, RBAP46 bound the transcription factor Sp1 in a PRC2-independent manner, resulting in the downregulation of reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a protein that suppresses tumor metastasis and angiogenesis [ 213 ].…”

Expression of p53, bax and bcl-2 and predictive value of fibrinogen, D-Dimer, and mean platelet volume in patients with acute cerebral infarction after intravenous thrombolysis

“…The bcl2 gene family is a complex network regulating apoptosis that some of its genes can inhibit apoptosis and others can induce it (30,31). Apoptosis is initiated by various stimuli and inhibited by increasing bcl-2 gene expression (32).…”