Guan Yanlei, Chen Ling, Bao Yijun, Pang Chao, Cui Run, Li Guangyu, Liu Jiyuan, Wang Yunjie
Department of Neurosurgery, First Affiliated Hospital of China Medical University Shenyang, Liaoning, P.R. China.
Department of Geratic Medicine, First Affiliated Hospital of China Medical University Shenyang, Liaoning, P.R. China.
Int J Clin Exp Pathol. 2015 Jan 1;8(1):727-34. eCollection 2015.
Several previous reports indicated that microRNA-504 (miR-504) has an oncogenic function through negatively regulating p53. On the other hand, a recent study revealed that miR-504 inhibits cancer cell proliferation through targeting CDK6 in hypopharyngeal squamous cell carcinoma (HSCC), suggesting the tumor suppressive role of this miRNA. However, the role of miR-504 in human malignant glioma remains unclear. Therefore, the aim of this study was to investigate the clinical significance of miR-504 expression in high pathological grade glioma. Quantitative real-time reverse transcriptive-PCR (qRT-PCR) was performed to examine miR-504 expression levels in 63 glioma tissues including 13 anaplastic astrocytomas (AA, WHO grade III) and 50 glioblastomas (GBM, WHO grade IV), as well as 10 non-neoplastic brain tissues. Associations between miR-504 expression and clinicopathological factors and prognosis of glioma patients were statistically analyzed. MiR-504 showed significant decreased expression levels both in AAs and GBMs relative to non-neoplastic brains (P ≤ 0.001, respectively). Additionally, low expression level of miR-504 was significantly associated with advanced WHO grade (P = 0.01). Moreover, Kaplan-Meier survival analysis showed that patients with low expression of miR-504 had significantly poor survival rate (P = 0.002). Cox regression analysis showed that miR-504 expression was independent prognosis-predicting factor for malignant glioma patients (P = 0.038; risk ration = 2.5). Our results suggest that miR-504 may be a prognostic predictor and be involved in tumorigencity as a tumor suppressor of malignant glioma.
先前的几份报告表明，微小RNA-504（miR-504）通过负调控p53发挥致癌作用。另一方面，最近一项研究显示，在下咽鳞状细胞癌（HSCC）中，miR-504通过靶向细胞周期蛋白依赖性激酶6（CDK6）抑制癌细胞增殖，提示该微小RNA具有肿瘤抑制作用。然而，miR-504在人类恶性胶质瘤中的作用仍不清楚。因此，本研究旨在探讨miR-504表达在高病理分级胶质瘤中的临床意义。采用定量实时逆转录聚合酶链反应（qRT-PCR）检测63例胶质瘤组织（包括13例间变性星形细胞瘤（AA，世界卫生组织III级）和50例胶质母细胞瘤（GBM，世界卫生组织IV级））以及10例非肿瘤性脑组织中miR-504的表达水平。对miR-504表达与胶质瘤患者临床病理因素及预后的相关性进行统计学分析。相对于非肿瘤性脑组织，miR-504在AA和GBM中的表达水平均显著降低（P值均≤0.001）。此外，miR-504低表达水平与世界卫生组织高级别显著相关（P = 0.01）。而且，Kaplan-Meier生存分析显示，miR-504低表达患者的生存率显著较低（P = 0.002）。Cox回归分析显示，miR-504表达是恶性胶质瘤患者独立的预后预测因素（P = 0.038；风险比= 2.5）。我们的结果表明，miR-504可能是一种预后预测指标，并作为恶性胶质瘤的肿瘤抑制因子参与肿瘤发生。
