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miR-144-3p 通过靶向 FZD7 发挥肿瘤抑制作用,并预测人脑胶质母细胞瘤的预后。

miR-144-3p serves as a tumor suppressor by targeting FZD7 and predicts the prognosis of human glioblastoma.

机构信息

Department of Neurosurgery, Linyi People's Hospital, Linyi, Shandong, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Sep;21(18):4079-4086.

Abstract

OBJECTIVE

Previous research indicated that miR-144-3p was associated with the regulation of the carcinogenic processes, but the role of miR-144-3p in glioblastoma (GBM) remains unclear. In this study, we aimed to analyze the role of miR-144-3p in GBM.

PATIENTS AND METHODS

The expression of miR-144-3p was measured in GBM tissues and adjacent non-malignant tissues using qRT-PCR. The correlation of miR-144-3p with clinicopathological features and prognosis was also analyzed. Cell proliferation, invasion, and migration assay were applied to assess the function of miR-144-3p in vitro. Bioinformatics prediction and luciferase assays were employed to identify the predicted microRNA (miRNA) which regulates Frizzled-7 (FZD7). The levels of FZD7 and FZD7 mRNA were determined by Western blot and RT-PCR.

RESULTS

The results showed that the miR-144-3p expression was significantly downregulated in tumor tissues and GBM cell lines compared with that in normal brain tissues and the normal human astrocytes. The levels of miR-144-3p were negatively correlated with the status of WHO grade and recurrence. Furthermore, patients with low serum levels of miR-144-3p had a significantly shorter median overall survival rate. Multivariate Cox regression analysis confirmed that low level of miR-144-3p expression predicted poor prognosis independently. Further function assays showed that miR-144-3p inhibited proliferation invasion and migration of GBM cells. Finally, miR-144-3p was demonstrated to bind to the wild-type 3' untranslated region of FZD7 but not with its mutant.

CONCLUSIONS

The results of the present study indicate that miR-144-3p suppresses tumor metastasis by targeting FZD7. This work also provides strong evidence that miR-144-3p is an independent prognostic factor for patients with GBM.

摘要

目的

先前的研究表明 miR-144-3p 与致癌过程的调节有关,但 miR-144-3p 在胶质母细胞瘤(GBM)中的作用尚不清楚。本研究旨在分析 miR-144-3p 在 GBM 中的作用。

患者与方法

采用 qRT-PCR 检测 GBM 组织及相邻非恶性组织中 miR-144-3p 的表达,分析 miR-144-3p 与临床病理特征和预后的相关性。体外细胞增殖、侵袭和迁移实验评估 miR-144-3p 的功能。采用生物信息学预测和荧光素酶报告基因实验鉴定调控 Frizzled-7(FZD7)的预测 miRNA(miRNA)。采用 Western blot 和 RT-PCR 检测 FZD7 及其 mRNA 的水平。

结果

结果表明,与正常脑组织和正常人星形胶质细胞相比,肿瘤组织和 GBM 细胞系中 miR-144-3p 的表达明显下调。miR-144-3p 的水平与 WHO 分级和复发状态呈负相关。此外,血清 miR-144-3p 水平较低的患者中位总生存率明显缩短。多变量 Cox 回归分析证实,低水平 miR-144-3p 表达独立预测预后不良。进一步的功能分析表明,miR-144-3p 抑制 GBM 细胞的增殖、侵袭和迁移。最后,miR-144-3p 被证明可以结合 FZD7 的野生型 3'非翻译区,但不能结合其突变型。

结论

本研究结果表明,miR-144-3p 通过靶向 FZD7 抑制肿瘤转移。本研究还为 miR-144-3p 是 GBM 患者独立预后因素提供了有力证据。

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