Department of Obstetrics and Gynecology, Linyi People's Hospital, Liny, Shandong, China.
Eur Rev Med Pharmacol Sci. 2017 Dec;21(24):5587-5593. doi: 10.26355/eurrev_201712_13999.
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.
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.
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.
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.
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。
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。
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。
本研究首次表明 miR-638 可能作为一种肿瘤抑制因子。在未来，miR-638 可能作为人类 CC 的治疗靶点和潜在的预后因素。
