第二军医大：miRNA文库筛选解开胆囊癌转移之谜

　　

第二军医大学研究者采用miRNA文库筛选新技术，发现促使胆囊癌转移的重要小RNA分子——MiR-20a。这一小RNA可能作为治疗胆囊癌的潜在靶点，其相关研究发表在《Journal of Hepatology》杂志上。

胆囊癌(GBC)是一种恶性肿瘤，恶性程度高、易早期转移、难于早期发现、对化疗药物不敏感等特点，因而解开胆囊癌的发病及转移机制将对治疗有很大的作用。

MiRNA参与许多癌症的发展，然而关于miRNA同 GBC调控关系的研究较少。上海第二军医大学研究者采用一种新的文库筛选方法，筛查GBC转移相关的miRNA，通过锐博生物提供的文库micrON™ miRNA mimics library（Ribobio.Co.Ltd） 在880种miRNA中进行筛选，最终确定17种miRNA影响着GBC的转移。进一步研究表明，上调miR-20a与相邻组织入侵、远距离转移及预后不良显著相关，且miR-20a高表达的GBC患者生存率较低。研究者发现患者体内TGF-β1大幅度的增加，而TGF-β1的增加导致miR-20a表达量的升高，这种miR-20a的异常表达能诱发上皮细胞间质转移和增加GBC细胞的转移。这一研究表明TGF-β1激活miR-20a/Smad7/β-catenin机制，调控着GBC的病发及恶化。因此miR-20a的表达在GBC转移过程中扮演着至关重要的角色，miR-20a有望为癌症的治疗提供新的靶点。

随着肿瘤研究的深入，siRNA和miRNA已经成为基因研究的重要工具。锐博生物经验丰富的核酸研发团队已在相关领域开展了广泛的研究，并将继续精进科技，不断提升，为相关研究做出更多的贡献。

请访问www.sirna.cn或拨打免费咨询热线400-6860075。

锐博生物推荐原文：

MiR-20a Triggers Metastasis of GallbladderCarcinoma.

Chang Y,Liu C,etal. J Hepatol. 2013 May 9. PMID:23665284
 
Abstract：BACKGROUND & AIMS: The dysfunction of miRNAs hasbeen demonstrated participating in the regulation of various tumordevelopments. However, whether miRNAs are involved in metastasisand progression of GBC remains obscure.

METHODS: A new designed gain-of-function miRNAs screeningtechnology was applied to filter out pro-metastatic miRNAs in GBC. Theirexpression in GBC tissues was validated by real-time PCR. The biologicalfunctions of miRNAs were intensively studied by transwell, immunoblot,immunohistochemical and in situ hybridization assays. Tumorigenicity and liver metastasis were further examined in nude mice.

RESULTS: Of 880 miRNAs, 17 were filtered out as the prominentmetastatic inducers for GBCs. Among them, the up-regulation of pro-metastatic miR-20a was closely associated with the local invasion,distant metastasis and poor prognosis of 67followed-up GBC patients clinically. Patients with higher miR-20a expression exhibited worse overall survival (OS,median OS time were 5 and 20 months, respectively) than the lower expressiongroup. The dramatically increased TGF-β1 level was found in GBC patients, whichwas responsible for the elevation of miR-20a. Theectopic expression of miR-20a could induceEpithelial-mesenchymal transition and enhance the metastasisof GBC cells in vitro and in vivo, through directly targeting the 3'UTR ofSmad7 and promoting nucleus translocation of β-catenin subsequently.Conversely, the blockage of miR-20a by specificantagomir effectively restored the expression of Smad7 and attenuatedTGF-β-induced cell metastasis.

CONCLUSIONS: TGF-β1-mediated activation of miR-20a/Smad7/β-cateninaxis plays a pivotal role in the pathogenesis and worse prognosis of GBCs,which may serve as a potential therapeutic target in the future.