miR-638 通过 Wnt/β-catenin 信号通路抑制宫颈癌转移，与宫颈癌患者的预后相关。

MiR-638 inhibits cervical cancer metastasis through Wnt/β-catenin signaling pathway and correlates with prognosis of cervical cancer patients.

机构信息

Department of Obstetrics and Gynecology, Linyi People's Hospital, Liny, Shandong, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Dec;21(24):5587-5593. doi: 10.26355/eurrev_201712_13999.

DOI:10.26355/eurrev_201712_13999

PMID:29271990

Abstract

OBJECTIVE

MiR‑638 has been demonstrated to be correlated with several tumor progressions. However, the exact role of miRNA-638 in cervical cancer (CC) has not been investigated. The aim of present study was to explore the prognostic value of miR-638 in patients with CC and analyze molecular mechanisms of miR-638 in CC progression.

PATIENTS AND METHODS

Real-time quantitative RT-PCR was performed to measure miR-638 expression level in 196 paired of CC and matched normal tissues, CC cell lines. The correlation of miR-638 with clinicopathological features and prognosis was analyzed. Furthermore, the effects of miR-638 on tumorigenicity of CC cells were evaluated by functional assays. Finally, Western blot was used to evaluate the activation of Wnt/β-catenin signaling pathway.

RESULTS

We found that miR-638 expression was downregulated in CC tissues and cell lines compared with the adjacent normal tissues and normal cell lines. In addition, low expressions of miR-638 were significantly associated with advanced FIGO stage (p =0.007), lymph node metastasis (p = 0.018) and vascular invasion (p = 0.002). Moreover, the results of Kaplan-Meier method showed that CC patients with lower miR-638 expression had significantly poorer overall survival (p = 0.0023) and progression-free survival (p = 0.0005). In a multivariate Cox model, we found that miR-638 expression was an independent prognostic factor for both overall survival and progression-free survival in patients with CC (both p = 0.001). In vitro assay showed that miR-638 overexpression suppressed cell migration and invasion of HeLa cells. The results of Western blot indicated that over-expression of miR-638 inhibited the activation of Wnt/β-catenin signaling pathway.

CONCLUSIONS

Our findings firstly showed that miR-638 might serve as a tumor suppressor. In the future, miR-638 might be regarded as a therapeutic target and a potential prognostic factor in human CC.

摘要

目的

已有研究表明 miR-638 与多种肿瘤进展相关。然而，miRNA-638 在宫颈癌（CC）中的具体作用尚未得到研究。本研究旨在探讨 miR-638 在 CC 患者中的预后价值，并分析 miR-638 在 CC 进展中的分子机制。

患者与方法

采用实时定量 RT-PCR 检测 196 对 CC 组织及其配对正常组织、CC 细胞系中 miR-638 的表达水平。分析 miR-638 与临床病理特征和预后的相关性。进一步通过功能实验评估 miR-638 对 CC 细胞致瘤性的影响。最后，采用 Western blot 检测 Wnt/β-catenin 信号通路的激活情况。

结果

我们发现 miR-638 在 CC 组织和细胞系中的表达水平低于相邻正常组织和正常细胞系。此外，miR-638 低表达与 FIGO 分期较晚（p=0.007）、淋巴结转移（p=0.018）和血管侵犯（p=0.002）显著相关。Kaplan-Meier 方法的结果表明，miR-638 表达较低的 CC 患者总生存期（p=0.0023）和无进展生存期（p=0.0005）明显较差。多因素 Cox 模型分析发现，miR-638 表达是 CC 患者总生存期和无进展生存期的独立预后因素（均 p=0.001）。体外实验表明，miR-638 过表达抑制 HeLa 细胞的迁移和侵袭。Western blot 结果表明，miR-638 过表达抑制 Wnt/β-catenin 信号通路的激活。