CREB5 promotes the proliferation and self-renewal ability of glioma stem cells

CREB5促进胶质瘤干细胞增殖和自我更新能力

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作者:Hyun-Jin Kim #, Hye-Min Jeon #, Don Carlo Batara, Seongsoo Lee, Suk Jun Lee, Jinlong Yin, Sang-Ik Park, Minha Park, Jong Bae Seo, Jinik Hwang, Young Joon Oh, Sung-Suk Suh, Sung-Hak Kim

Abstract

Glioblastoma multiforme (GBM) is the most fatal form of brain cancer in humans, with a dismal prognosis and a median overall survival rate of less than 15 months upon diagnosis. Glioma stem cells (GSCs), have recently been identified as key contributors in both tumor initiation and therapeutic resistance in GBM. Both public dataset analysis and direct differentiation experiments on GSCs have demonstrated that CREB5 is more highly expressed in undifferentiated GSCs than in differentiated GSCs. Additionally, gene silencing by short hairpin RNA (shRNA) of CREB5 has prevented the proliferation and self-renewal ability of GSCs in vitro and decreased their tumor forming ability in vivo. Meanwhile, RNA-sequencing, luciferase reporter assay, and ChIP assay have all demonstrated the closely association between CREB5 and OLIG2. These findings suggest that targeting CREB5 could be an effective approach to overcoming GSCs.

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