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miR-484/MAP2/c-Myc 正调控环路在神经胶质瘤中通过 ERK1/2 信号促进肿瘤起始特性。

miR-484/MAP2/c-Myc-positive regulatory loop in glioma promotes tumor-initiating properties through ERK1/2 signaling.

机构信息

Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China.

Department of Neurosurgery, the First Affiliated Hospital of Gannan Medical University, No. 23 Youth Road, Ganzhou, 341000, Jiangxi, People's Republic of China.

出版信息

J Mol Histol. 2018 Apr;49(2):209-218. doi: 10.1007/s10735-018-9760-9. Epub 2018 Feb 26.

DOI:10.1007/s10735-018-9760-9
PMID:29480405
Abstract

Glioma is the most common intracranial malignant tumor. Cancer stem cells (CSCs) are resistant to chemotherapy and radiotherapy, and are closely related to cancer metastasis and recurrence. In this study, we aimed to explore the effect of miR-484 on glioma stemness and the underlying mechanism involved. miR-484 enhanced glioma tumor-initiating properties in vitro and in vivo. Moreover, miR-484 was shown to directly target MAP2, resulting in activation of ERK1/2 signaling and promotion of stemness in glioma. The ERK1/2 signaling facilitated the formation of a miR-484/MAP2/c-Myc positive feedback loop in glioma. High miR-484 expression predicted a poor prognosis for glioma patients, and high MAP2 expression predicted a good prognosis for glioma patients. Low miR-484 expression and high MAP2 expression was associated with the best prognosis in glioma. Our study suggests that miR-484 and MAP2 can be utilized as predictors for the clinical diagnosis and prognosis of glioma, and miR-484 and MAP2 are potential targets for the treatment of glioma.

摘要

神经胶质瘤是最常见的颅内恶性肿瘤。癌症干细胞(CSCs)对化疗和放疗具有抗性,并且与癌症转移和复发密切相关。在这项研究中,我们旨在探讨 miR-484 对神经胶质瘤干性的影响及其涉及的潜在机制。miR-484 增强了体外和体内神经胶质瘤肿瘤起始特性。此外,miR-484 被证明可以直接靶向 MAP2,导致 ERK1/2 信号的激活,并促进神经胶质瘤的干性。ERK1/2 信号促进了神经胶质瘤中 miR-484/MAP2/c-Myc 正反馈环的形成。高 miR-484 表达预示着神经胶质瘤患者的预后不良,而高 MAP2 表达预示着神经胶质瘤患者的预后良好。低 miR-484 表达和高 MAP2 表达与神经胶质瘤的最佳预后相关。我们的研究表明,miR-484 和 MAP2 可作为神经胶质瘤临床诊断和预后的预测因子,miR-484 和 MAP2 是治疗神经胶质瘤的潜在靶点。

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