Sohlh1 Modulates the Stemness and Differentiation of Glioma Stem‐Like Cells by Inactivation of Wnt/β‐Catenin Signalling Pathway via <scp>SFRP1</scp>

Glioma stem-like cells (GSLCs) are tumour initiating cells that drive tumorigenesis and progression through self-renewal and various differentiation potencies. Therefore, the identification of genes required for GSLC stemness and differentiation is vital for the development of novel targeted therapies. Sohlh1 belongs to the superfamily of bhlh transcription factors and serves as a tumour suppressor in glioma. The role of Sohlh1 in GSLCs remains unknown. Here, we demonstrated that Sohlh1 functioned through the SFRP1/Wnt/β-catenin signalling pathway and led to the consequent suppression of GSLC stemness and the promotion of GSLC differentiation in vitro and in vivo. Moreover, Sohlh1 could directly bind to the promoter of SFRP1 and promote its transcriptional activity. SFRP1 mediated the effects of Sohlh1 on GSLC stemness and differentiation. Clinically, we observed a significant inverse correlation between Sohlh1 and Nestin expression levels, and a positive correlation between Sohlh1 and SFRP1 expression in glioma tissues. Collectively, our findings suggest an important role of the Sohlh1/SFRP1/Wnt/β-catenin pathway in regulating GSLC stemness and differentiation, suggesting potential therapeutic targets for glioma.