小分子诱导胶质瘤细胞向神经元样细胞的转化

Conversion of glioma cells into neuron-like cells by small molecules.

作者信息

Yi Yongjun, Che Wenqiang, Xu Ping, Mao Chuxiao, Li Zhizhong, Wang Qingsong, Lyu Jun, Wang Xiangyu

机构信息

Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Guangzhou 510632, P.R. China.

Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou 510630, P.R. China.

出版信息

iScience. 2024 Oct 2;27(11):111091. doi: 10.1016/j.isci.2024.111091. eCollection 2024 Nov 15.

Currently, researchers are exploring the conversion of astrocytes into functional mature neurons and gradually exploring the conversion of glioma into neurons. We report that SLCDS (SB431542, LDN193189, CHIR99021, DAPT, and SKL2001) has been shown to convert human glioma cells into mature neuron-like cells. The converted cells exhibited upregulation of DCX, TuJ1, MAP2, NeuN, and GAD67, while the expressions of EGFR, PDGFR, Ki67, and vimentin were inhibited. The nTFs, such as NeuroD1 and Sox2, were upregulated, along with TF genes associated with neurogenesis and tumor suppression. We have finally confirmed that overexpressing nTFs can induce the conversion of glioma cells into neuronal cells. This study demonstrates that SLCDS can activate the expression of nTFs in human glioma cells and induce the conversion of human glioma cells into neuron-like cells. Additionally, SLCDS inhibits the expressions of EGFR, PDGFR, Ki67, and Vimentin in gliomas. Our findings offer a potential approach for treating glioma.

目前，研究人员正在探索将星形胶质细胞转化为功能性成熟神经元，并逐步探索将胶质瘤转化为神经元。我们报告称，SLCDS（SB431542、LDN193189、CHIR99021、DAPT和SKL2001）已被证明可将人胶质瘤细胞转化为成熟的神经元样细胞。转化后的细胞表现出双皮质素（DCX）、微管相关蛋白2（MAP2）、神经元核抗原（NeuN）和谷氨酸脱羧酶67（GAD67）表达上调，而表皮生长因子受体（EGFR）、血小板衍生生长因子受体（PDGFR）、增殖细胞核抗原（Ki67）和波形蛋白的表达受到抑制。神经分化因子1（NeuroD1）和性别决定区Y框蛋白2（Sox2）等神经转录因子（nTFs）上调，同时与神经发生和肿瘤抑制相关的转录因子基因也上调。我们最终证实，过表达nTFs可诱导胶质瘤细胞转化为神经细胞。本研究表明，SLCDS可激活人胶质瘤细胞中nTFs的表达，并诱导人胶质瘤细胞转化为神经元样细胞。此外，SLCDS可抑制胶质瘤中EGFR、PDGFR、Ki67和波形蛋白的表达。我们的研究结果为治疗胶质瘤提供了一种潜在的方法。