RPA3 通过激活 PI3K-AKT-mTOR 通路促进脑胶质瘤的增殖、迁移和侵袭。
RPA3 promotes the proliferation, migration, and invasion of gliomas by activating the PI3K-AKT-mTOR pathway.
机构信息
Graduate School, Hebei Medical University, Shijiazhuang, 050017, China.
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, China.
出版信息
Cell Mol Biol (Noisy-le-grand). 2023 May 31;69(5):80-86. doi: 10.14715/cmb/2023.69.5.14.
Gliomas are the most common primary malignant brain tumors, with a poor prognosis and high mortality, and there is no effective treatment regimen. A number of studies have shown that replication protein A3 (RPA3) can regulate DNA replication and that the abnormal expression of RPA3 can lead to genomic instability and induce the development of a variety of tumors. However, the relationship between RPA3 and gliomas and the mechanism of action remains unclear. In this study, we investigated the role of RPA3 in the development of gliomas and the possible mechanism. The Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases were used to analyze the expression level of RPA3 and its correlation with clinical prognosis. A univariate Cox regression model was established to predict the prognosis of glioma patients and analyze the correlation between RPA3 and immune cell infiltration and activation. Immunohistochemistry, RT-PCR, and Western blot (WB) were used to detect the expression of RPA3 in glioma specimens. After knocking down and overexpressing RPA3 with plasmids, effects on glioma cell proliferation, migration and invasive capacity were investigated in vitro. The possible molecular mechanisms were analyzed using WB. Results showed that the expression of RPA3 in glioma tissue and cells was significantly higher than that in normal glial cells and was positively correlated with the poor prognosis of patients with gliomas. The overexpression of RPA3 expression activated the phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of the rapamycin (mTOR) pathway by promoting the phosphorylation of PI3K, AKT, and mTOR, thereby promoting the proliferation, migration and invasion of glioma cells. In conclusion, RPA3 is highly expressed in gliomas and promotes the proliferation, migration and invasion of gliomas by activating the PI3K-AKT-mTOR pathway. Therefore, RPA3 may be a prognostic biomarker and therapeutic target for gliomas.
神经胶质瘤是最常见的原发性恶性脑肿瘤，预后不良，死亡率高，目前尚无有效的治疗方案。许多研究表明，复制蛋白 A3（RPA3）可以调节 DNA 复制，而 RPA3 的异常表达会导致基因组不稳定，并诱导多种肿瘤的发生。然而，RPA3 与神经胶质瘤之间的关系及其作用机制尚不清楚。在本研究中，我们研究了 RPA3 在神经胶质瘤发生发展中的作用及其可能的机制。我们使用中国神经胶质瘤基因组图谱（CGGA）、癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）分析了 RPA3 的表达水平及其与临床预后的相关性。建立了单变量 Cox 回归模型来预测神经胶质瘤患者的预后，并分析了 RPA3 与免疫细胞浸润和激活的相关性。免疫组织化学、RT-PCR 和 Western blot（WB）用于检测神经胶质瘤标本中 RPA3 的表达。用质粒敲低和过表达 RPA3 后，在体外研究其对神经胶质瘤细胞增殖、迁移和侵袭能力的影响。用 WB 分析了可能的分子机制。结果表明，RPA3 在神经胶质瘤组织和细胞中的表达明显高于正常神经胶质细胞，与神经胶质瘤患者的不良预后呈正相关。RPA3 的过表达通过促进 PI3K、AKT 和 mTOR 的磷酸化激活磷脂酰肌醇 3-激酶（PI3K）-AKT-雷帕霉素靶蛋白（mTOR）通路，从而促进神经胶质瘤细胞的增殖、迁移和侵袭。总之，RPA3 在神经胶质瘤中高表达，并通过激活 PI3K-AKT-mTOR 通路促进神经胶质瘤的增殖、迁移和侵袭。因此，RPA3 可能是神经胶质瘤的预后标志物和治疗靶点。
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