miR-625 suppresses tumour migration and invasion by targeting IGF2BP1 in hepatocellular carcinoma
miR-625 suppresses tumour migration and invasion by targeting IGF2BP1 in hepatocellular carcinoma
复制标题
miR-625通过靶向IGF2BP1抑制肝细胞癌中的肿瘤迁移和侵袭
DOI：
10.1038/onc.2014.35
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发表时间：
2015-02-19
期刊：
影响因子：
8
通讯作者：
Yun, J-P
中科院分区：
文献类型：
--
作者：
Zhou, X.;Zhang, C. Z.;Yun, J-P
肝细胞癌（HCC）是世界范围内最常见的恶性肿瘤之一，也是癌症相关死亡的第三大原因。肿瘤转移是高死亡率的主要原因之一。microRNA与HCC转移有关。在这项研究中，我们发现miR-625在HCC样本中频繁下调。miR-625的减少与淋巴结和远处转移（P= 0.013）、门静脉浸润（P= 0.036）、肿瘤淋巴结转移（TNM）分期（P= 0.027）和不利的总生存期（P= 0.003）显著相关。与原发性肿瘤相比，门静脉转移瘤中miR-625的表达显著降低。miR-625在肝癌细胞中的重新表达在体外和体内均能显著抑制细胞的迁移和侵袭。从机制上讲，miR-625被证实直接下调IGF 2 mRNA结合蛋白1（IGF 2BP 1），其表达与HCC细胞系和组织中miR-625的水平呈负相关。IGF 2BP 1高表达常发生在HCC组织中，且与预后不良相关。通过siRNA敲低内源性IGF 2BP 1表现出与过表达miR-625相似的效果，而过表达IGF 2BP 1（无3′-UTR）则消除了miR-625介导的转移抑制。干扰PTEN/HSP 27通路有助于miR-625介导的转移抑制。综上所述，我们的数据表明，miR-625可能作为一种抗转移的miRNA发挥作用，通过调节IGF 2BP 1/PTEN通路在HCC进展中发挥重要作用。新发现的miR-625/IGF 2BP 1轴代表了HCC治疗的新的潜在治疗靶点。
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and the third leading cause of cancer-related deaths worldwide. Tumour metastasis is one of the major causes of high mortality. microRNAshave been implicated in HCC metastasis. In this study, we found that miR-625 was frequently downregulated in HCC samples. A decrease in miR-625 was significantly correlated with lymph node anddistance metastasis (P= 0.013), the presence of portal venous invasion (P= 0.036), tumor-node-metastasis (TNM) stage (P= 0.027) and unfavourable overall survival (P= 0.003). Compared with primary tumours, miR-625 expression was markedly reduced in portal venous metastatic tumours. Re-expression of miR-625 in HCC cells was remarkably effective in suppressing cell migration andinvasiveness in vitro and in vivo. Mechanistically, miR-625 was confirmed to downregulate IGF2 mRNA-binding protein 1 (IGF2BP1) directly, the expression of which was inversely correlated with the level of miR-625 in HCC cell lines and tissues. High expression of IGF2BP1 was frequently found in HCC samples, and associated with poor prognosis. Knockdown of endogenous IGF2BP1 by siRNA exhibited similar effects as the overexpression of miR-625, whereas overexpression of IGF2BP1 (without the 3′-UTR) abrogated miR-625-mediated metastasis inhibition. Interference of the PTEN/HSP27 pathway contributed to miR-625-mediated metastasis inhibition. Taken together, our data suggest that miR-625 might function as an antimetastatic miRNA to have an important role in HCC progression by modulating the IGF2BP1/PTEN pathway. The newly identified miR-625/IGF2BP1 axis represents a new potential therapeutic target for HCC treatment.