胶质母细胞瘤（GBM）是一种最常见的原发性恶性脑肿瘤，其特点是高增殖和迁移潜能，导致肿瘤具有高浸润性。然而，GBM增殖和迁移的潜在机制尚未完全阐明。在本研究中，首先，我们使用RNA-seq技术和生物信息学技术筛选出C-X-C基序配体1（CXCL1）作为与增殖相关的基因。外源性胶质细胞源性神经营养因子（GDNF）通过sqPCR和ELISA测定，诱导大鼠C6胶质瘤细胞的增殖并上调CXCL1水平。然后，我们利用慢病毒载体（CXCL1-RNAi）方法操控CXCL1表达。通过这种方法，C6细胞的增殖减少，表明CXCL1在这些细胞中发挥关键作用。我们假设外源性GDNF促进了NF-κB核转位，并通过Western blot和免疫荧光分析CXCL1与NF-κB的相互作用。此外，我们使用NF-κB的磷酸化抑制剂BAY 11-7082阐明了GDNF对CXCL1的作用是否由NF-κB介导。这些结果证明GDNF通过激活NF-κB/CXCL1信号通路增强了大鼠C6胶质瘤细胞的增殖。总之，这些研究不仅揭示了外源性GDNF促进C6胶质瘤细胞增殖的作用机制，还可能为恶性胶质瘤的治疗提供了新的生物学靶点。版权：©2023王等。本文采用知识共享署名许可协议，允许在任何媒介下自由使用、分发和再现，前提是原作者和出处得到了适当的认可。

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor that is characterized by its high proliferative and migratory potential, leading to a high invasiveness of this tumor type. However, the underlying mechanism of GBM proliferation and migration has not been fully elucidated. In this study, at first, we used RNA-seq together with bioinformatics technology to screen for C-X-C motif ligand 1 (CXCL1) as a proliferation-related gene. And exogenous glial cell line-derived neurotrophic factor (GDNF) induced proliferation and up-regulated the level of CXCL1 in rat C6 glioma cells determined by sqPCR and ELISA. Then, we manipulated the CXCL1 expression by using a lentiviral vector (CXCL1-RNAi) approach. By this, the proliferation of C6 cells was decreased, suggesting that CXCL1 plays a key role in proliferation in these cells. We hypothesized that exogenous GDNF promoted NF-κB nuclear translocation and therefore, analyzed the interaction of CXCL1 with NF-κB by Western Blot and immunofluorescence. Additionally, we used BAY 11-7082, a phosphorylation inhibitor of NF-κB, to elucidate NF-κB mediated the effect of GDNF on CXCL1. These results demonstrated that GDNF enhanced the proliferation of rat C6 glioma cells through activating the NF-κB/CXCL1 signaling pathway. In summary, these studies not only revealed the mechanism of action of exogenous GDNF in promoting the proliferation of C6 glioma cells but may also provide a new biological target for the treatment of malignant glioma.Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.