Department of Neurosurgery, The First Affiliated Hospital of Xi'an JiaoTong University, No. 277 Yanta West Road, Xi'an City, Shaanxi Province, 710061, China; Department of Neurosurgery, Baoji Centre Hospital of Shanxi Province, No. 8 Jiangtan Road, Baoji City, Shaanxi Province, 721008, China.
Department of Hematology and Immunology, Yan'an University Affiliated Hospital, Yan'an, Shaanxi Province, 716000, China.
Eur J Pharmacol. 2019 Nov 15;863:172643. doi: 10.1016/j.ejphar.2019.172643. Epub 2019 Sep 4.
As the most fatal disease in human central nerve system, glioblastoma has attracted increasing attention. Unfortunately, the prognosis for patients with glioblastoma still quite unfavorable. Recent years, circular RNAs (circRNAs) have been identified to be associated with carcinogenesis due to their abnormal expression. However, the detailed molecular mechanism of circRNAs in regulating cancer progression is still unclear. This study focused on the potential mechanism of circ-PITX1 in glioblastoma. Herein, circ-PITX1 was found to be upregulated in glioblastoma and could mediate glioblastoma tissues and cell lines. Functionally, downregulation of circ-PITX1 hampered cell proliferation and accelerated cell apoptosis. Through mechanism investigation, we identified the cytoplasmic localization of circ-PITX1 and its molecular sponge role. The interactions between circ-PITX1 and miR-379-5p as well as between miR-379-5p and MAP3K2 were demonstrated. Thus, we confirmed that circ-PITX1 exerted as a competing endogenous RNA (ceRNA) in glioblastoma by sponging miR-379-5p to elevate MAP3K2 expression. Rescue assays demonstrated that MAP3K2 rescued the proliferation and apoptosis mediated by the silencing of circ-PITX1. Collectively, our study elucidated a novel molecular pathway and its functions in glioblastoma.
作为人类中枢神经系统中最致命的疾病,脑胶质瘤受到了越来越多的关注。不幸的是,脑胶质瘤患者的预后仍然相当不利。近年来,由于circRNAs 的异常表达,已经发现它们与肿瘤发生有关。然而,circRNAs 调节癌症进展的详细分子机制尚不清楚。本研究专注于 circ-PITX1 在脑胶质瘤中的潜在机制。研究发现,circ-PITX1 在脑胶质瘤中上调,并可介导脑胶质瘤组织和细胞系。功能上,circ-PITX1 的下调抑制了细胞增殖并加速了细胞凋亡。通过机制研究,我们确定了 circ-PITX1 的细胞质定位及其分子海绵作用。证明了 circ-PITX1 与 miR-379-5p 以及 miR-379-5p 与 MAP3K2 之间的相互作用。因此,我们证实 circ-PITX1 通过海绵 miR-379-5p 来升高 MAP3K2 的表达,作为脑胶质瘤中的竞争性内源 RNA (ceRNA) 发挥作用。挽救实验表明,MAP3K2 挽救了 circ-PITX1 沉默介导的增殖和凋亡。总之,我们的研究阐明了脑胶质瘤中一个新的分子途径及其功能。