POLR2J is a potential biomarker for abnormal tumor progression, vorinostat sensitization, immune infiltration, and prognosis of glioblastoma multiform

Glioma is one of the most primary malignant brain tumors, and glioblastoma multiform (GBM) is the most common and highly aggressive glioma. Most GBM are high malignant, poor prognosis, 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, we elucidated that the maximal overexpression of DNA-directed RNA polymerase II subunit J-1 (POLR2J) was observed in GBM compared with normal tissues among all cancer types, and high expression of POLR2J or its co-expressed genes predicted poor outcome of GBM patients. DNA replication were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited the proliferation and triggered cell cycle G1/G0 phase arrest of GBM cells. HDAC inhibitors, such as vorinostat, are identified as effective agents against GBM. We showed that POLR2J silence activated UPR and significantly enhanced anti-GBM activity of vorinostat via suppressing cell proliferation and inducing apoptosis. In addition, POLR2J promoted epithelial-mesenchymal transition (EMT) and the metastatic potentials of GBM cells. Furthermore, POLR2J expression was negatively relevant to the number of B cells, neutrophil, myeloid dendritic cells, CD4 + T cells and etc. Meanwhile, the expression of POLR2J was negatively correlative to the expression of immunotherapy-related genes. Our study confirmed a novel oncogene POLR2J in GBM progression as well as provided a promising strategy for the chemotherapy and immunotherapy of GBM treatment.