Zhi Sujuan, Chen YanRu, Xiao Yunling, Liu Lanlan, Feng Xiaoning, Liu Xuyue, Shen Ying, Zhang RuiHong, Hao Jing
Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
J Cell Mol Med. 2025 May;29(10):e70599. doi: 10.1111/jcmm.70599.
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.
胶质瘤干细胞（GSLCs）是通过自我更新和多种分化潜能驱动肿瘤发生和进展的肿瘤起始细胞。因此，鉴定GSLC干性和分化所需的基因对于开发新型靶向治疗至关重要。Sohlh1属于bhlh转录因子超家族，在胶质瘤中作为肿瘤抑制因子发挥作用。Sohlh1在GSLCs中的作用尚不清楚。在此，我们证明Sohlh1通过SFRP1/Wnt/β-连环蛋白信号通路发挥作用，从而在体外和体内抑制GSLC干性并促进GSLC分化。此外，Sohlh1可直接结合SFRP1的启动子并促进其转录活性。SFRP1介导了Sohlh1对GSLC干性和分化的影响。临床上，我们观察到胶质瘤组织中Sohlh1与巢蛋白表达水平呈显著负相关，而Sohlh1与SFRP1表达呈正相关。总体而言，我们的研究结果表明Sohlh1/SFRP1/Wnt/β-连环蛋白通路在调节GSLC干性和分化中起重要作用，提示胶质瘤潜在的治疗靶点。
