PSMC2/E2F1 Axis Promotes the Development and Progression of Glioma [post]

Xuchen Qi, Qin Lu, Dajiang Xie, Junhui Lv, Yiwei Liu, Shuxu Yang, Yirong Wang, Xueyong Zheng
2021 unpublished
Background Glioma is the most common type of malignant brain tumor with limited treatment strategy and poor prognosis. Proteasome 26S subunit ATPase 2 (PSMC2) is a key member of the 26S proteasome 19S regulatory subunit, whose role in glioma is still not clear. In this context, we aim to explore the role of PSMC2 in glioma in vitro and in vivo. Methods Expression of PSMC2 in in glioma tissues and normal tissues are detected by immunohistochemical (IHC) analysis. The proliferation assays (MTT
more » ... tion assays (MTT assay and Celigo cell counting assay), flow cytometry and migration assays (wound-healing assay and Transwell) are used to detect the effects of PSMC2 knockdown on glioma cells. The influence of PSMC2 knockdown on tumor growth in vivo was evaluated by mice xenograft models. In addition, the downstream target of PSMC2 is determined by human GeneChip and Ingenuity Pathway Analysis (IPA). Results PSMC2 is overexpressed in glioma tissues than normal tissues. Moreover, knockdown of PSMC2 can inhibit the proliferation, migration and arrest cell cycle in G2 phase of glioma cells. Additionally, PSMC2 knockdown promotes glioma cell apoptosis by increasing expression of caspase3, caspase8, IGFBP-1, while reducing expression of IGF-I, Survivin, TRAILR-4. In vivo findings reveal that PSMC2 knockdown inhibit the tumorigenicity of glioma cells. Furthermore, downstream of PSMC2 is explored, identifying E2F transcription factor 1 (E2F1) as a potential target. Notably, E2F1 knockdown exhibits similar effects on the development of glioma with PSMC2, which could strengthen the inhibition effects of PSMC2 knockdown on glioma synergistically. Conclusions PSMC2 is closely associated with glioma development by targeting E2F1, and might be considered as a novel therapeutic target in patients with glioma.
doi:10.21203/rs.3.rs-141267/v1 fatcat:6hjfvmpwezegvdyabnswequ3ti