Department of Neurosurgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, 230001, People's Republic of China.
Anhui Key Laboratory of Brain Function and Diseases, Hefei, Anhui, 230001, People's Republic of China.
Mol Neurobiol. 2024 Sep;61(9):6556-6571. doi: 10.1007/s12035-024-04002-0. Epub 2024 Feb 7.
Exosomes play a crucial role in regulating crosstalk between tumor and tumor stem-like cells through their cargo molecules. Circular RNAs (circRNAs) have recently been demonstrated to be critical factors in tumorigenesis. This study focuses on the molecular mechanism by which circRNAs from glioma stem-like cell (GSLC) exosomes regulate glioblastoma (GBM) tumorigenicity. In this study, we validated that GSLC exosomes accelerated the malignant phenotype of GBM. Subsequently, we found that circZNF800 was highly expressed in GSLC exosomes and was negatively associated with GBM patients. CircZNF800 promoted GBM cell proliferation and migration and inhibited GBM cell apoptosis in vitro. Silencing circZNF800 could improve the GBM xenograft model survival rate. Mechanistic studies revealed that circZNF800 activated the PIEZO1/Akt signaling pathway by sponging miR-139-5p. CircZNF800 derived from GSLC exosomes promoted GBM cell tumorigenicity and predicted poor prognosis in GBM patients. CircZNF800 has the potential to serve as a promising target for further therapeutic exploration.
外泌体通过其携带的分子在肿瘤和肿瘤类干细胞之间的串扰调控中发挥关键作用。环状 RNA（circRNA）最近被证明是肿瘤发生的关键因素。本研究关注的是来自神经胶质瘤干细胞（GSLC）外泌体的 circRNA 通过何种分子机制调节神经胶质瘤（GBM）的致瘤性。在这项研究中，我们验证了 GSLC 外泌体加速了 GBM 的恶性表型。随后，我们发现 circZNF800 在 GSLC 外泌体中高表达，与 GBM 患者呈负相关。CircZNF800 在体外促进了 GBM 细胞的增殖和迁移，抑制了 GBM 细胞的凋亡。沉默 circZNF800 可以提高 GBM 异种移植模型的存活率。机制研究表明，circZNF800 通过海绵吸附 miR-139-5p 激活了 PIEZO1/Akt 信号通路。来自 GSLC 外泌体的 circZNF800 促进了 GBM 细胞的肿瘤发生，并预测了 GBM 患者的不良预后。CircZNF800 有可能成为进一步治疗探索的有前途的靶点。
Zotero 插件
