Bulk and single cells transcriptomes with experimental validation identify USP18 as a novel glioma prognosis and proliferation indicator

Yang Chen; Ren Li; Ziao Li; Biao Yang; Jianhang He; Jiayu Li; Peize Li; Zihan Zhou; Yongqiang Wu; Yuanli Zhao; Geng Guo

doi:10.3892/etm.2024.12517

Bulk and single cells transcriptomes with experimental validation identify USP18 as a novel glioma prognosis and proliferation indicator

Exp Ther Med. 2024 Mar 26;27(5):229. doi: 10.3892/etm.2024.12517. eCollection 2024 May.

Authors

Yang Chen¹, Ren Li², Ziao Li¹, Biao Yang¹, Jianhang He¹, Jiayu Li¹, Peize Li¹, Zihan Zhou¹, Yongqiang Wu³, Yuanli Zhao⁴, Geng Guo³

Affiliations

¹ Department of Neurosurgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
² School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
³ Department of Emergency, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
⁴ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P.R. China.

Abstract

The mechanism by which ubiquitin-specific protease 18 (USP18) (enzyme commission: 3.4.19.12) inhibition in cancer promotes cell pyroptosis via the induction of interferon (IFN)-stimulated genes has been recently demonstrated. It is also known that USP18 influences the epithelial-mesenchymal transition of glioma cells. In the present study, the upregulation of USP18 in glioma was revealed through bulk transcriptome analysis, which was associated with poor prognosis in patients with glioma. Furthermore, USP18 levels affected the response to immunotherapy in patients with glioma. Single-cell transcriptome and enrichment analyses demonstrated that USP18 was associated with type 1 IFN responses in glioma T cells. To demonstrate the effect of USP18 expression levels on glioma cells, USP18 expression was knocked down in U251 and U87MG ATCC cell lines. A subsequent Cell Counting Kit-8 assay revealed that glioma cell viability was significantly decreased 4 days after USP18 knockdown. In addition, the knockdown of USP18 expression significantly inhibited the clonogenicity of U251 and U87MG ATCC cells. In conclusion, the present study demonstrated that knockdown of USP18 expression inhibited the proliferation of glioma cells, which may be mediated by the effect of USP18 on the IFN-I response.

Keywords: glioma; oncology; prognostic biomarker; proliferation; ubiquitin-specific protease 18.

Grants and funding

Funding: The present study was supported by the National Natural Science Foundation of China (grant no. 81201991), the Basic Research Program of Shanxi Province (grant no. 202103021224400), the Key Medical Scientific Research Projects of Shanxi (grant no. 2021XM35) and the Four ‘Batches’ Innovation Project of Invigorating Medical through Science and Technology of Shanxi (grant no. 2022RC07).