miR-455-3p serves as prognostic factor and regulates the proliferation and migration of non-small cell lung cancer through targeting HOXB5
miR-455-3p serves as prognostic factor and regulates the proliferation and migration of non-small cell lung cancer through targeting HOXB5
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DOI：
10.1016/j.bbrc.2017.11.123
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发表时间：
2018-01-01
影响因子：
3.1
通讯作者：
Zhang, Mingzhi
中科院分区：
文献类型：
--
作者：
Gao, Xianzheng;Zhao, Huaying;Zhang, Mingzhi
MicroRNA（miRs）在人类肿瘤的发生和发展中起重要作用。最近发现miR-455- 3 p可以在多种人类癌症中发挥肿瘤抑制因子的作用。然而，其在非小细胞肺癌（NSCLC）中的表达和生物学作用仍然是难以捉摸的。在本研究中，我们发现miR-455- 3 p在NSCLC组织和细胞系中显著下调。卡方检验显示miR-455 - 3 p表达与低分化癌和晚期肿瘤相关（P <0. 05）。Kaplan-Meier曲线显示，miR-455- 3 p低表达组5年生存率较低（P = 0.029）。单变量和多变量分析表明，低miR-455- 3 p表达是总生存期的不利预后因素。功能获得和功能丧失研究显示，miR-455- 3 p在体外抑制细胞增殖和迁移。计算机算法和双荧光素酶报告基因分析显示，miR-455- 3 p直接靶向并抑制NSCLC中的HOXB 5。进一步的研究表明，HOXB 5的敲除可以减弱miR-455- 3 p下调对细胞增殖和迁移的影响。综上所述，我们的研究结果首次表明，miR-455- 3 p在NSCLC中下调，并与NSCLC患者的不良预后相关。此外，miR-455- 3 p通过直接靶向NSCLC进展中的HOXB 5而发挥肿瘤抑制剂的作用，并可用作NSCLC治疗的潜在靶点。(C)2017爱思唯尔公司All rights reserved.
MicroRNAs (miRs) have been reported to play significantly roles in the initiation and progression of human cancers. miR-455-3p has been recently found could function as tumor suppressor in various human cancers. However, its expression and biological role in non-small cell lung cancer (NSCLC) remains elusive. In this study, we found miR-455-3p was markedly downregulated in NSCLC tissues and cell lines. Chi-square test to analyze the correlations between miR-455-3p expression and clinicopathological features revealed that miR-455-3p expression was correlated with poorly differentiated cancer and advanced tumor stage (P < 0.05). Kaplan-Meier curve revealed that low expression of miR-455-3p was correlated with shorter 5-year survival time (P = 0.029). Univariate and multivariate analyses identified low miR-455-3p expression was an unfavorable prognostic factor for overall survival. Gain-of function and loss-of-function studies revealed that miR-455-3p inhibits cell proliferation and migration in vitro. Computer algorithm and dual-luciferase reporter assay revealed that miR-455-3p directly targets and suppresses HOXB5 in NSCLC. Further studies demonstrated that knockdown of HOXB5 attenuated the effect of miR-455-3p downregulation on cell proliferation and migration. Taken together, our results for the first time suggested that miR-455-3p was downregulated in NSCLC and was correlated with the poor prognosis of NSCLC patients. Also, miR-455-3p functions as tumor suppressor by directly targeting HOXB5 in NSCLC progression and may be used as a potential target for NSCLC treatment. (C) 2017 Elsevier Inc. All rights reserved.