miR-455-3p 通过靶向 FAM83F 作为一个预后标志物抑制食管鳞癌细胞的增殖和侵袭。
MiR-455-3p acts as a prognostic marker and inhibits the proliferation and invasion of esophageal squamous cell carcinoma by targeting FAM83F.
机构信息
Department of Oncology, Three Gorges University People's Hospital, The First People's Hospital of Yichang, Yichang, Hubei Province, China.
出版信息
Eur Rev Med Pharmacol Sci. 2017 Jul;21(14):3200-3206.
OBJECTIVE
The aim of the current study was to elucidate the role of miR-455-3p in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and its prognostic value in patients with ESCC.
PATIENTS AND METHODS
Expression levels of miR-455-3p and FAM83F mRNA in ESCC tissues and adjacent normal tissues were detected by quantitative RT-PCR. The X2-test was used to assess miR-455-3p expression on clinicopathological parameters. The association with overall survival of patients was analyzed by Kaplan-Meier survival analysis. Cox's multivariate regression model was performed to identify independent prognostic factors of overall survival. The effect of miR-455-3p on proliferation was evaluated by kit-8 (CCK-8), and cell invasion was evaluated by transwell assays. The molecular target of miR-455-3p was identified using a computer algorithm and confirmed experimentally. Furthermore, the effect of miR-455-3p up-regulation on FAM83F expression was examined by Western blot.
RESULTS
miRNA-455-3p was significantly increased in ESCC tissues and cell lines. Also, miR-455-3p expression was significantly associated with histological grade, lymph nodes metastasis and clinical stage (all p < 0.05). The patients with low miR-455-3p expression had shorter survival time than those with high miR-455-3p expression. Furthermore, univariate and multivariate analysis identified low miR-455-3p expression as an unfavorable prognostic factor for overall survival. Moreover, transfection with the miR-455-3p mimic enhanced the cell proliferation and invasion in ESCC cells. Luciferase reporter assays confirmed that miR-455-3p binding to the 3'-UTR regions of FAM83F inhibited the expression of FAM83F in ESCC cells. Western blot confirmed that overexpression of miR-455-3p resulted in down-regulation of FAM83F in ESCC cells.
CONCLUSIONS
Our findings indicate that miR-455-3p plays an anti-oncogenic role in the development of ESCC by downregulation of FAM83F and could be an independent marker for predicting the clinical outcome of ESCC patients.
目的
本研究旨在阐明 miR-455-3p 在食管鳞状细胞癌（ESCC）发病机制中的作用及其在 ESCC 患者中的预后价值。
方法
采用实时定量 RT-PCR 检测 ESCC 组织和相邻正常组织中 miR-455-3p 和 FAM83F mRNA 的表达水平。X2 检验评估 miR-455-3p 表达与临床病理参数的关系。采用 Kaplan-Meier 生存分析评估患者总生存率的相关性。采用 Cox 多因素回归模型确定总生存率的独立预后因素。通过 CCK-8 试剂盒评估 miR-455-3p 对增殖的影响，通过 Transwell 测定评估细胞侵袭。利用计算机算法鉴定 miR-455-3p 的分子靶标，并通过实验进行验证。此外，通过 Western blot 检测 miR-455-3p 上调对 FAM83F 表达的影响。
结果
miR-455-3p 在 ESCC 组织和细胞系中显著升高。此外，miR-455-3p 的表达与组织学分级、淋巴结转移和临床分期显著相关（均 p<0.05）。miR-455-3p 低表达的患者生存时间明显短于 miR-455-3p 高表达的患者。此外，单因素和多因素分析均表明 miR-455-3p 低表达是总生存的不利预后因素。此外，miR-455-3p 模拟物的转染增强了 ESCC 细胞的增殖和侵袭。荧光素酶报告基因检测证实，miR-455-3p 结合 FAM83F 的 3'-UTR 区域抑制了 ESCC 细胞中 FAM83F 的表达。Western blot 证实，miR-455-3p 的过表达导致 ESCC 细胞中 FAM83F 的下调。
结论
本研究结果表明，miR-455-3p 通过下调 FAM83F 在 ESCC 的发生发展中发挥抑癌作用，可能成为预测 ESCC 患者临床预后的独立标志物。
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