MiR-146b-5p functions as a suppressor miRNA and prognosis predictor in non-small cell lung cancer.
MiR-146b-5p functions as a suppressor miRNA and prognosis predictor in non-small cell lung cancer.
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MiR-146b-5p 在非小细胞肺癌中充当抑制 miRNA 和预后预测因子
DOI：
10.7150/jca.16961
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发表时间：
2017
影响因子：
3.9
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Li Y;Zhang H;Dong Y;Fan Y;Li Y;Zhao C;Wang C;Liu J;Li X;Dong M;Liu H;Chen J
非小细胞肺癌（NSCLC）是全球癌症相关死亡的主要原因。然而，科学尚未能够实质性地改善肺癌患者的预后。越来越多的证据表明microRNAs（miRNAs）在调节肿瘤的发生和转移中起着关键作用。在78例NSCLC标本中，使用实时RT-PCR检测了先前显示在肿瘤发展中起作用的6种miRNA（miR-146 b-5 p、miR-128 b、miR-21、miR-221、miR-34 a和Let-7a）的表达。结果显示，miR-146 b-5 p低表达患者的中位和平均生存时间显著短于miR-146 b-5 p高表达患者（分别为33.00和30.44个月vs 42.0和36.90个月;对数秩检验P=0.048），因此，miR-146 b-5 p低表达水平与NSCLC患者的不良预后相关。单因素考克斯风险回归分析显示，miR-146 b-5 p表达水平倾向于成为NSCLC的一个显著预后指标（校正风险比=0.482，95%CI：1.409 ~ 29.593，P=0.016）。多因素考克斯比例风险回归分析显示，miR-146 b-5 p表达水平是影响NSCLC患者预后的独立因素（hazard ratio=0.259，95%CI：0.083-0.809，P=0.020）。此外，研究了miR-146 b-5 p和miR-146 b-3 p对NSCLC细胞体外生长和侵袭的影响。我们的研究结果表明，异位表达的miR-146 b-5 p抑制细胞增殖，克隆形成，迁移/侵袭，并诱导G1期阻滞在体外，但不诱导细胞凋亡;而强制表达的miR-146 b-3 p对细胞的生长和转移没有显着的影响。进一步的实验表明，miR-146 b-5 p在体外可降低MMP 16和TRAF 6的mRNA水平，并与人NSCLC组织中TRAF 6的表达呈负相关。在小鼠模型中，Ago-miR-146 b-5 p可显著抑制肺癌裸鼠移植瘤的生长。总之，我们的研究结果表明，miR-146 b-5 p在NSCLC中作为抑制性miRNA和预后预测因子发挥作用。
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. However, science has not yet been able to substantially improve the prognosis of lung cancer patients. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor development and metastasis. Expression of six miRNAs previously shown to play roles in tumor development (miR-146b-5p, miR-128b, miR-21, miR-221, miR-34a, and Let-7a) in other tumor types was examined using real-time RT-PCR in 78 specimens of NSCLC. The results revealed that patients with low expression of miR-146b-5p had significant shorter median and mean survival time than those with high miR-146b-5p expression (33.00 and 30.44 months versus 42.0 and 36.90 months, respectively; log-rank test P=0.048), thus low miR-146b-5p expression level was associated with poor prognosis in NSCLC patients. Univariate Cox hazard regression analysis demonstrated that miR-146b-5p expression levels tended to be a significant prognostic indicator of NSCLC (adjusted hazard ratio=0.482, 95% CI: 1.409- 29.593, P=0.016). Multivariate Cox proportional hazard regression analysis showed that miR-146b-5p expression levels were an independent prognostic factor for NSCLC patients (hazard ratio=0.259, 95% CI: 0.083-0.809, P=0.020). Furthermore, the effects of miR-146b-5p and miR-146b-3p on NSCLC cell growth and invasion in vitro were investigated. Our findings demonstrate that ectopic expression of miR-146b-5p suppressed cell proliferation, clonogenicity, migration/ invasion and also induced G1 arrest in vitro, but did not induce cell apoptosis; whereas enforced expression of miR-146b-3p did not have a significant effect on cell growth and metastasis. Further experiments indicated that miR-146b-5p could reduce mRNA levels of MMP16 and TRAF6 in vitro and was negatively related to the expression of TRAF6 in human NSCLC tissues. In a mouse model, Ago-miR-146b-5p could significantly inhibit the growth of lung cancer xenografts in nude mice. In conclusion, our findings demonstrate that miR-146b-5p functions as a suppressor miRNA and prognosis predictor in NSCLC.
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影响因子：
3.4
作者：
Wei, Bin;Huang, Qiao Ying;Zhong, Xiao Gang
通讯作者：
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作者：
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影响因子：
15.9
作者：
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DOI：
10.1016/j.bbrc.2015.10.062
发表时间：
2015-11-27
影响因子：
3.1
作者：
Wang, Ping;Guo, Xueyan;He, Shuixiang
通讯作者：
He, Shuixiang