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. 2023 Dec;45(12):1623-1632.
doi: 10.1007/s13258-023-01468-5. Epub 2023 Oct 19.

SUZ12 inhibition attenuates cell proliferation of glioblastoma via post-translational regulation of CDKN1B

Sojin Kim  1 , Sungsin Jo  2 , Sun Ha Paek  3 , Sang Soo Kang  4 , Heekyoung Chung  5   6
Affiliations

SUZ12 inhibition attenuates cell proliferation of glioblastoma via post-translational regulation of CDKN1B

Sojin Kim et al. Genes Genomics. 2023 Dec.

Abstract

Background: Human gliomas are aggressive brain tumors characterized by uncontrolled cell proliferation. Differential expression of Polycomb repressive complex 2 (PRC2) has been reported in various subtypes of glioma. However, the role of PRC2 in uncontrolled growth in glioma and its underlying molecular mechanisms remain to be elucidated.

Objective: We aimed to investigate the functional role of PRC2 in human glioblastoma cell growth by silencing SUZ12, the non-catalytic core component of PRC2.

Methods: Knockdown of SUZ12 was achieved by infecting T98G cells with lentivirus carrying sequences specifically targeting SUZ12 (shSUZ12). Gene expression was examined by quantitative PCR and western analysis. The impact of shSUZ12 on cell growth was assessed using a cell proliferation assay. Cell cycle distribution was analyzed by flow cytometry, and protein stability was evaluated in cycloheximide-treated cells. Subcellular localization was examined through immunofluorescence staining and biochemical cytoplasmic-nuclear fractionation. Gene expression analysis was also performed on human specimens from normal brain and glioblastoma patients.

Results: SUZ12 knockdown (SUZ12 KD) led to widespread decrease in the PRC2-specific histone mark, accompanied by a slowdown of cell proliferation through G1 arrest. In SUZ12 KD cells, the degradation of CDKN1B protein was reduced, resulting from alterations in the MYC-SKP2-CDKN1B axis. Furthermore, nuclear localization of CDKN1B was enhanced in SUZ12 KD cells. Analysis of human glioblastoma samples yielded increased expression of EZH2 and MYC along with reduced CDKN1B compared to normal human brain tissue.

Conclusion: Our findings suggest a novel role for SUZ12 in cell proliferation through post-translational regulation of CDKN1B in glioblastoma.

Keywords: CDKN1B; Glioblastoma; PRC2; Post-translational regulation; SUZ12.

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