POLR2J expression promotes glioblastoma malignancy by regulating oxidative stress and the STAT3 signaling pathway

Xiao-Li Zheng; Zhi-Di Li; Kai-Zhi Luo; Yang-Ling Li; Ye-Han Liu; Shu-Ying Shen; Fei-Yan Shen; Wan-Yan Li; Guo-Qing Chen; Chong Zhang; Ling-Hui Zeng

doi:10.62347/JEWM7691

POLR2J expression promotes glioblastoma malignancy by regulating oxidative stress and the STAT3 signaling pathway

Am J Cancer Res. 2024 May 15;14(5):2037-2054. doi: 10.62347/JEWM7691. eCollection 2024.

Authors

Xiao-Li Zheng^{1

2}, Zhi-Di Li^{2

3}, Kai-Zhi Luo^{2

4}, Yang-Ling Li⁵, Ye-Han Liu^{2

3}, Shu-Ying Shen⁶, Fei-Yan Shen^{2

3}, Wan-Yan Li², Guo-Qing Chen¹, Chong Zhang^{1

2}, Ling-Hui Zeng^{1

2}

Affiliations

¹ Taizhou Boai Hospital, Affiliated Luqiao Hospital, School of Medicine, Hangzhou City University Hangzhou 310015, Zhejiang, China.
² Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University Hangzhou 310015, Zhejiang, China.
³ Department of Pharmacology, Zhejiang University Hangzhou 310058, Zhejiang, China.
⁴ College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Engineering of Zhejiang Province, Zhejiang University of Technology Hangzhou 310014, Zhejiang, China.
⁵ Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine Hangzhou 310006, Zhejiang, China.
⁶ College of Pharmaceutical Sciences, Hangzhou First People's Hospital, Zhejiang Chinese Medical University Hangzhou 310006, Zhejiang, China.

Abstract

Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.

Keywords: Glioblastoma; POLR2J; cell migration; prognosis; proliferation.