miR-1181 的下调预示着鼻咽癌患者预后不良，并通过调节 Wnt/β-catenin 信号通路促进细胞增殖和转移。

Down-regulation of miR-1181 indicates a dismal prognosis for nasopharyngeal carcinoma and promoted cell proliferation and metastasis by modulating Wnt/β-catenin signaling.

机构信息

Department of ENT, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Feb;23(3):1077-1086. doi: 10.26355/eurrev_201902_16996.

DOI:10.26355/eurrev_201902_16996

PMID:30779075

Abstract

OBJECTIVE

Our study aimed to investigate the expression pattern, clinicopathological feature and prognostic role of miR-1181 in nasopharyngeal carcinoma (NPC), and to determine the functional effects and potential mechanism of miR-1181 in NPC.

PATIENTS AND METHODS

The expression levels of miR-1181 were determined in NPC tissues and cell lines by RT-PCR. The clinical data were interpreted by chi-square test, univariate analysis, and multivariate analysis. The effect of PVT1 on proliferation was evaluated by CCK-8 and colony formation assays, and migration and invasion ability were evaluated by transwell and wound-healing assays. The association between miR-1181 and Wnt/β-catenin pathway was analyzed by Western blot.

RESULTS

We found that miR-1181 expression was significantly down-regulated in both NPC tissues and cell lines. Low expression of miR-1181 was significantly associated with N stage (p=0.013), clinical stage (p=0.037) and grade (p=0.033). Clinical assays showed that patients with low miR-1181 expression had shorter overall survival time than those with high miR-1181 expression (p=0.0007). Multivariate analysis revealed that miR-1181 expression was independently associated with the overall survival. Functional investigations indicated that overexpression of miR-1181 suppressed NPC cells proliferation, migration and invasion. Mechanistically, forced miR-1181 expression suppressed the activity of Wnt/β-catenin pathway.

CONCLUSIONS

Our findings proved that miR-1181 may serve as a candidate prognostic biomarker and target for new therapies in NPC patients.

摘要

目的

本研究旨在探讨 miR-1181 在鼻咽癌（NPC）中的表达模式、临床病理特征和预后作用，并确定 miR-1181 在 NPC 中的功能效应和潜在机制。

患者与方法

通过 RT-PCR 测定 NPC 组织和细胞系中 miR-1181 的表达水平。通过卡方检验、单因素分析和多因素分析解释临床数据。通过 CCK-8 和集落形成实验评估 PVT1 对增殖的影响，通过 Transwell 和划痕愈合实验评估迁移和侵袭能力。通过 Western blot 分析 miR-1181 与 Wnt/β-catenin 通路的关联。

结果

我们发现 miR-1181 在 NPC 组织和细胞系中的表达均显著下调。miR-1181 的低表达与 N 分期（p=0.013）、临床分期（p=0.037）和分级（p=0.033）显著相关。临床分析表明，miR-1181 低表达的患者总生存时间短于 miR-1181 高表达的患者（p=0.0007）。多因素分析显示，miR-1181 的表达与总生存独立相关。功能研究表明，miR-1181 的过表达抑制 NPC 细胞的增殖、迁移和侵袭。机制上，强制表达 miR-1181 抑制了 Wnt/β-catenin 通路的活性。