Department of Neurosurgery, Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Road, Xi'an, 710004, Shaanxi, China.
Department of Internal Medicine 2, Shaanxi Provincial Tumor Hospital, The Affiliated Hospital of Xi'an Jiaotong Univesity, Xi'an, 710061, Shaanxi, China.
J Mol Histol. 2021 Oct;52(5):1007-1020. doi: 10.1007/s10735-021-09993-x. Epub 2021 Jun 28.
Glioma remains the most common malignant tumors in the central nervous system and often has poor prognosis. In recent years, it has been gradually revealed that non-coding RNA effects glioma progression. In this study, we aimed to investigate the significance of circular RNA TLK1 (Circ-TLK1) in predicting the survival of glioma patients as well as its role in glioma development via both in-vitro and in-vivo experiments. We found that Circ-TLK1 was conspicuously up-regulated in glioma tissues compared with adjacent normal tissues, and the up-regulated Circ-TLK1 was significantly correlated with glioma patients' larger tumor volume and higher grades. Functionally, Circ-TLK1 over-expression facilitated glioma growth, migration and invasion, inhibited cell apoptosis, and accelerated PANX1/MAPK/ERK expression, while Circ-TLK1 low expression had the opposite effects. In addition, bioinformatics analysis showed that miR-17-5p was a potential target of Circ-TLK1 and targeted at PANX1. Furthermore, through dual luciferase viability assay, Circ-TLK1 acted as a competing endogenous RNA by sponging miR-17-5p, which targeted and inhibited PANX1/MAPK/ERK expression. MiR-17-5p overexpression mitigated glioma progression, which was significantly inhibited with Circ-TLK1 upregulation. In conclusion, this study confirmed a novel axis of Circ-TLK1-miR-17-5p-PANX1 in modulating glioma development, providing more references for glioma diagnosis and targeted therapy.
神经胶质瘤仍然是中枢神经系统最常见的恶性肿瘤，通常预后不良。近年来，逐渐揭示出非编码 RNA 影响神经胶质瘤的进展。在这项研究中，我们旨在通过体外和体内实验，研究环状 RNA TLK1（Circ-TLK1）在预测神经胶质瘤患者生存中的意义及其在神经胶质瘤发生中的作用。我们发现，与相邻正常组织相比，神经胶质瘤组织中 Circ-TLK1 显著上调，上调的 Circ-TLK1 与神经胶质瘤患者更大的肿瘤体积和更高的分级显著相关。功能上，Circ-TLK1 过表达促进神经胶质瘤的生长、迁移和侵袭，抑制细胞凋亡，并加速 PANX1/MAPK/ERK 表达，而 Circ-TLK1 低表达则有相反的作用。此外，生物信息学分析表明，miR-17-5p 是 Circ-TLK1 的一个潜在靶点，靶向 PANX1。此外，通过双荧光素酶活性测定，Circ-TLK1 通过海绵吸附 miR-17-5p 作为竞争性内源性 RNA，靶向并抑制 PANX1/MAPK/ERK 表达。miR-17-5p 过表达减轻了神经胶质瘤的进展，而 Circ-TLK1 的上调则显著抑制了这一进展。总之，本研究证实了 Circ-TLK1-miR-17-5p-PANX1 调节神经胶质瘤发生的新轴，为神经胶质瘤的诊断和靶向治疗提供了更多的参考。
