Decreased expression of miR-126 correlates with metastatic recurrence of hepatocellular carcinoma

Decreased expression of miR-126 correlates with metastatic recurrence of hepatocellular carcinoma
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DOI:
10.1007/s10585-013-9569-6
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发表时间:
2013-06-01
影响因子:
4
通讯作者:
Peng, Zhihai
Peng, Zhihai
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Hongyuan;Miao, Ruizheng;Peng, Zhihai

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肝移植为研究肝细胞癌(HCC)转移提供了一个有吸引力的模型。基于微阵列数据,我们之前发现miR-126在肝癌后复发患者的肿瘤组织中的表达低于未复发患者。在本研究中,我们采用实时荧光定量PCR检测了68例肝细胞癌肝移植患者肝细胞癌样本中miR-126的表达,并分析其与患者临床病理特征和预后的相关性。此外,我们通过实验分析探讨了miR-126在HCC转移中的作用。我们发现,与未复发患者相比,肝癌后复发患者肿瘤组织中miR-126水平较低(p = 0.009)。miR-126在HCC中的低表达与肿瘤复发(p = 0.011)和患者生存差(p = 0.009)显著相关。功能研究表明,miR-126的异位表达在体外显著抑制HCC细胞的迁移、侵袭、增殖和集落形成,并在体内抑制实验性肺定植。我们的研究揭示了miR-126的下调在HCC转移中起重要作用,并提示miR-126在HCC预后预测和治疗中的潜在应用。
The liver transplant (LT) situation represents an attractive model for studying hepatocellular carcinoma (HCC) metastasis. Based on microarray data, we previously found that miR-126 expression was lower in tumor tissues of patients with post-LT HCC recurrence compared with non-recurrence. In this study, we examined the expression of miR-126 in HCC samples from 68 patients who had undergone LT using quantitative real-time PCR and analyzed its correlation with clinicopathological features and prognosis of patients. Furthermore, we performed experimental analyses to explore the involvement of miR-126 in HCC metastasis. We found that miR-126 levels were lower in tumor tissues of patients with post-LT HCC recurrence in comparison to patients with no-recurrence (p = 0.009). Lower expression of miR-126 in HCC was associated significantly with tumor recurrence (p = 0.011) and poor survival (p = 0.009) of patients. Functional studies indicated that ectopic expression of miR-126 significantly inhibits HCC cells migration, invasion, proliferation and colony formation in vitro, and suppresses experimental lung colonization in vivo. Our study revealed that down-regulation of miR-126 plays an important role in HCC metastasis, and suggest a potential application of miR-126 in prognosis prediction and HCC treatment.