Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Road, Xi'an City, 710004, China.
Health Management Department, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Road, Xi'an City, 710004, China.
Clin Transl Oncol. 2023 May;25(5):1277-1286. doi: 10.1007/s12094-022-03022-3. Epub 2022 Dec 1.
Cancer stem cells or cancer stemness has been confirmed to a major obstacle for glioma progression and it has also been reported that circRNAs play an important part in cancer progression. This study mainly focuses on revealing the role of circRPPH1 and the underlying mechanisms in glioma cell stemness.
In vitro experiment including RT-qPCR, Western blot, sphere-formation analysis, and ALDH1 activity, and in vivo tumorigenesis experiments were performed to evaluate the effects of circRPPH1 on glioma cell stemness. Luciferase reporter, ChIP, and DNA pull-down analysis were used to reveal the underlying mechanisms.
It was found that circRPPH1 level was upregulated in glioma cell spheres and facilitated the stemness of glioma cells; C-FOS transcriptionally activated circRPPH1 expression via directly binding to circRPPH1 promoter in glioma cells. Moreover, circRPPH1 promoted the stemness of glioma cells dependent on c-FOS-mediated transcriptional activation.
This study indicates that c-Fos-activated circRPPH1 contributes to glioma stemness and provides a potential target for glioma progression based on the c-FOS/circRPPH1 regulatory axis.
癌症干细胞或癌症干性已被证实是胶质瘤进展的主要障碍，有报道称 circRNAs 在癌症进展中发挥重要作用。本研究主要集中在揭示 circRPPH1 在神经胶质瘤细胞干性中的作用及其潜在机制。
通过 RT-qPCR、Western blot、球体形成分析和 ALDH1 活性分析以及体内肿瘤发生实验，评估 circRPPH1 对神经胶质瘤细胞干性的影响。利用荧光素酶报告基因、染色质免疫沉淀和 DNA 下拉分析揭示其潜在机制。
研究发现，circRPPH1 在神经胶质瘤细胞球体中上调，并促进神经胶质瘤细胞的干性；在神经胶质瘤细胞中，C-FOS 通过直接结合 circRPPH1 启动子转录激活 circRPPH1 的表达。此外，circRPPH1 依赖 c-FOS 介导的转录激活促进神经胶质瘤细胞的干性。
本研究表明，c-Fos 激活的 circRPPH1 有助于神经胶质瘤干细胞的干性，并基于 c-FOS/circRPPH1 调节轴为神经胶质瘤的进展提供了一个潜在的治疗靶点。
