Department of Oncology, Three Gorges University People's Hospital, The First People's Hospital of Yichang, Yichang, Hubei Province, China.
Eur Rev Med Pharmacol Sci. 2017 Jul;21(14):3200-3206.
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.
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.
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.
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.
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。
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。
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。
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。
