Deng Yifan, Li Yue, Fang Qi, Luo Honghai, Zhu Gang
Department of Neurosurgery, Huizhou Municipal Central Hospital Huizhou 516000, Guangdong, P. R. China.
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University Harbin 150001, Heilongjiang, P. R. China.
Am J Cancer Res. 2018 Nov 1;8(11):2238-2253. eCollection 2018.
In recent years, changes in microRNA (miRNA) expression have been detected in almost all human cancer types, including glioblastoma (GBM). Dysregulation of miRNAs may play tumor-suppressing or oncogenic roles in the initiation and progression of GBM, and may be involved in the regulation of multiple pathological behaviors. Therefore, identifying the clinical value and functional role of GBM-related miRNAs may provide effective therapeutic targets for the treatment of patients with this fatal malignancy. Dysregulation of miR-744 has been identified in several human cancer types. However, to the best of our knowledge, little is known concerning the expression pattern and biological roles of miR-744 in GBM. In this study, we found that miR-744 was significantly downregulated in GBM tissues and cell lines. Decreased miR-744 expression was significantly correlated with the Karnofsky Performance Scale (KPS) and World Health Organization (WHO) grade in GBM patients. miR-744 upregulation inhibited the proliferation, colony formation, migration, and invasion, in addition to inducing apoptosis of GBM cells . Inhibition of miR-744 had the opposite effect on these behaviors in GBM cells. Additionally, miR-744 attenuated the tumor growth of GBM cells . Furthermore, NIN1/RPN12 binding protein1 homolog () was identified as a direct target gene of miR-744 in GBM cells. was confirmed to be upregulated in GBM tissues, and this was inversely correlated with upregulation of miR-744 expression. Moreover, knockdown exhibited similar inhibitory effects as miR-744 overexpression in GBM cells. Notably, recovered expression counteracted the tumor-suppressing roles of miR-744 in the malignant phenotypes of GBM cells. Taken together, these results demonstrate that miR-744 directly targets NOB1 to inhibit the aggressive behaviors of GBM cells. Hence, the miR-744/ axis may be useful in the identification of novel therapies for GBM patients.
近年来,在几乎所有人类癌症类型中都检测到了微小RNA(miRNA)表达的变化,包括胶质母细胞瘤(GBM)。miRNA的失调可能在GBM的发生和发展中发挥肿瘤抑制或致癌作用,并可能参与多种病理行为的调节。因此,确定与GBM相关的miRNA的临床价值和功能作用可能为治疗这种致命恶性肿瘤的患者提供有效的治疗靶点。在几种人类癌症类型中已发现miR-744失调。然而,据我们所知,关于miR-744在GBM中的表达模式和生物学作用知之甚少。在本研究中,我们发现miR-744在GBM组织和细胞系中显著下调。miR-744表达降低与GBM患者的卡氏功能状态量表(KPS)和世界卫生组织(WHO)分级显著相关。miR-744上调抑制了GBM细胞的增殖、集落形成、迁移和侵袭,此外还诱导了GBM细胞凋亡。抑制miR-744对GBM细胞的这些行为有相反的作用。此外,miR-744减弱了GBM细胞的肿瘤生长。此外,NIN1/RPN12结合蛋白1同源物()被确定为GBM细胞中miR-744的直接靶基因。在GBM组织中被证实上调,并且这与miR-744表达上调呈负相关。此外,在GBM细胞中,敲低表现出与miR-744过表达相似的抑制作用。值得注意的是,恢复的表达抵消了miR-744在GBM细胞恶性表型中的肿瘤抑制作用。综上所述,这些结果表明miR-744直接靶向NOB1以抑制GBM细胞的侵袭行为。因此,miR-744/轴可能有助于为GBM患者确定新的治疗方法。