2010年3月21日在线发表在《自然-细胞生物学》Nature Cell Biology发表了来自上海市肿瘤研究所/上海交通大学肿瘤研究所癌基因及相关基因国家重点实验室研究人员获得了microRNA与肝癌转移的最新研究成果。
MicroRNA是一类21~25个碱基的小分子非编码RNA，存在于各种真核生物中。MicroRNA主要通过促进靶mRNA的降解或抑制其翻译过程而发挥调控作用，广泛参与细胞增殖、凋亡、代谢及分化等过程。MicroRNA的异常表达与肿瘤的发生、发展及演进有着极为密切的关系。基因组不稳定性是恶性肿瘤的基本特征，在癌发生发展过程中经常伴随染色体的扩增或缺失，从而导致癌基因的激活或抑癌基因的失活。许多microRNA分子定位于癌染色体变异区内，可作为癌基因或抑癌基因而在癌变过程中发挥重要作用。
该研究中，作者在肝癌染色体变异区内鉴定了肝癌转移促进因子miR-151，发现染色体8q24.3位点的扩增导致了miR-151及其宿主基因FAK在肝癌中的高表达；miR-151过表达显著增加肝癌细胞的迁移与侵袭能力，并促进肝癌细胞发生肝内转移；鉴定出RhoGDIA是miR-151下游靶基因，介导miR-151的促肝癌转移功能；发现miR-151与宿主基因FAK协同作用活化Rac, cdc42及Rho GTPase，进而促进肝癌细胞的迁移、侵袭与转移。研究组通过利用antagomir（由广州市锐博生物科技有限公司合成）抑制miRNA的表达，从而使肿瘤细胞转移得到抑制。
生物谷推荐原文出处：
Nature Cell Biology doi:10.1038/ncb2039
Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA.
Ding J, Huang S, Wu S, Zhao Y, Liang L, Yan M, Ge C, Yao J, Chen T, Wan D, Wang H, Gu J, Yao M, Li J, Tu H, He X.
[1] State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China. [2] These authors contributed equally to this work.
Recurrent chromosomal aberrations are often observed in hepatocellular carcinoma (HCC), but little is known about the functional non-coding sequences, particularly microRNAs (miRNAs), at the chromosomal breakpoints in HCC. Here we show that 22 miRNAs are often amplified or deleted in HCC. MicroRNA-151 (miR-151), a frequently amplified miRNA on 8q24.3, is correlated with intrahepatic metastasis of HCC. We further show that miR-151, which is often expressed together with its host gene FAK, encoding focal adhesion kinase, significantly increases HCC cell migration and invasion in vitro and in vivo, mainly through miR-151-5p, but not through miR-151-3p. Moreover, miR-151 exerts this function by directly targeting RhoGDIA, a putative metastasis suppressor in HCC, thus leading to the activation of Rac1, Cdc42 and Rho GTPases. In addition, miR-151 can function synergistically with FAK to enhance HCC cell motility and spreading. Thus, our findings indicate that chromosome gain of miR-151 is a crucial stimulus for tumour invasion and metastasis of HCC.
