Zhou Jiang, Wang Chengbin, Liu Yingliang, Cui Daming, Wang Zhenlin, Jiang Yang, Gao Liang
Department of Neurosurgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 200072, Shanghai, China.
Department of Neurosurgery, Ningbo Medical Center Lihuili hospital, Ningbo, China.
Cancer Cell Int. 2022 Nov 17;22(1):359. doi: 10.1186/s12935-022-02753-1.
Glioblastoma (GBM) is the most common primary malignant tumor in the brain, and its robust proliferation and invasion abilities reduce the survival time of patients. Circular RNAs (circRNAs) play an essential role in various tumors, such as regulating tumor cell proliferation, apoptosis, invasion, metastasis, and other progressive phenotypes through different mechanisms. Finding novel circRNAs may significantly contribute to the prognosis of GBM and provide the basis for the targeted therapy of GBM. In this study, we found circPTPRF is a novel circRNA that has never been studied, which was highly expressed in GBM and is closely related to poor patient prognoses. After knockdown or overexpression in glioma cell lines (U87 and LN229) and glioma stem cells (GSCs), we identified that circPTPRF could promote proliferation, invasion, and neurospheres formation abilities of GBM via in vitro and in vivo experiments. Mechanisms, miR-1208 was confirmed as a target of circPTPRF, and miR-1208 can also target the 3'UTR of YY1, and they were proved by luciferase reporter, western blotting (WB), qPCR and RNA immunoprecipitation (RIP) assays. The following rescue experiments demonstrated that circPTPRF was a miR-1208 sponge for upregulating YY1 expression to promote proliferation, invasion and neurosphere formation abilities of GBM in vitro. In conclusion, the circPTPRF/miR-1208/YY1 axis can regulate GBM progression. CircPTPRF may play an essential role in GBM diagnosis and prognostic prediction and be an important molecular target for GBM therapy.
胶质母细胞瘤（GBM）是最常见的原发性脑恶性肿瘤，其强大的增殖和侵袭能力缩短了患者的生存时间。环状RNA（circRNA）在各种肿瘤中发挥着重要作用，例如通过不同机制调节肿瘤细胞的增殖、凋亡、侵袭、转移及其他进展性表型。发现新的circRNA可能对GBM的预后有显著贡献，并为GBM的靶向治疗提供依据。在本研究中，我们发现circPTPRF是一种从未被研究过的新型circRNA，它在GBM中高表达，且与患者的不良预后密切相关。在胶质瘤细胞系（U87和LN229）和胶质瘤干细胞（GSCs）中进行敲低或过表达后，通过体外和体内实验，我们确定circPTPRF可促进GBM的增殖、侵袭及神经球形成能力。机制方面，miR - 1208被证实为circPTPRF的靶点，并且miR - 1208也可靶向YY1的3'UTR，这通过荧光素酶报告基因、蛋白质免疫印迹（WB）、定量聚合酶链反应（qPCR）和RNA免疫沉淀（RIP）实验得到证实。随后的拯救实验表明，circPTPRF作为miR - 1208的海绵，上调YY1表达，从而在体外促进GBM的增殖、侵袭及神经球形成能力。总之，circPTPRF/miR - 1208/YY1轴可调节GBM的进展。circPTPRF可能在GBM诊断和预后预测中发挥重要作用，并且是GBM治疗的重要分子靶点。
