MicroRNA-1246 enhances migration and invasion through CADM1 in hepatocellular carcinoma.
MicroRNA-1246 enhances migration and invasion through CADM1 in hepatocellular carcinoma.
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DOI：
10.1186/1471-2407-14-616
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发表时间：
2014-08-27
期刊：
影响因子：
3.8
通讯作者：
Zhao RC
中科院分区：
文献类型：
--
作者：
Sun Z;Meng C;Wang S;Zhou N;Guan M;Bai C;Lu S;Han Q;Zhao RC
microRNA 的异常表达已被证明在肝癌的发生和进展中发挥着至关重要的作用。 miR-1246在高侵袭能力细胞系中的表达量显着高于低侵袭能力细胞系。 Transwell小室（8-uM孔径；Costar）用于体外迁移和invison分析。双荧光素酶报告基因构建和双荧光素酶报告基因测定以鉴定 miR-1246 的靶标。通过免疫组织化学染色评估CADM1表达。收集患者的临床表现、治疗情况和生存情况进行统计分析。抑制miR-1246可有效减少肝细胞癌细胞系的迁移和侵袭。生物信息学和荧光素酶报告分析表明，miR-1246 特异性靶向细胞粘附分子 1 的 3'-UTR 并调节其表达。 CADM1 的下调增强了 HCC 细胞系的迁移和侵袭。此外，在肝癌患者的肿瘤组织中，miR-1246的表达与CADM1呈负相关，miR-1246的高表达联合CADM1的低表达可能是1期肝癌患者的危险因素。我们的研究表明，miR-1246 通过下调 CADM1，增强 HCC 细胞的迁移和侵袭。本文的在线版本 (doi:10.1186/1471-2407-14-616) 包含补充材料，可供授权用户使用。
The aberrant expression of microRNAs has been demonstrated to play a crucial role in the initiation and progression of hepatocarcinoma. miR-1246 expression in High invasive ability cell line than significantly higher than that in low invasive ability cell line. Transwell chambers (8-uM pore size; Costar) were used in the in vitro migration and invison anssay. Dual luciferase reporter gene construct and Dual luciferase reporter assay to identify the target of miR-1246. CADM1 expression was evaluated by immunohistochemistric staining. The clinical manifestations, treatments and survival were collected for statistical analysis. Inhibition of miR-1246 effectively reduced migration and invasion of hepatocellular carcinoma cell lines. Bioinformatics and luciferase reporter assay revealed that miR-1246 specifically targeted the 3′-UTR of Cell adhesion molecule 1 and regulated its expression. Down-regulation of CADM1 enhanced migration and invasion of HCC cell lines. Furthermore, in tumor tissues obtained from liver cancer patients, the expression of miR-1246 was negatively correlated with CADM1 and the high expression of miR-1246 combined with low expression of CADM1 might serve as a risk factor for stage1 liver cancer patients. Our study showed that miR-1246, by down-regulation CADM1, enhances migration and invasion in HCC cells. The online version of this article (doi:10.1186/1471-2407-14-616) contains supplementary material, which is available to authorized users.
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