2010年3月21日在線發(fā)表在《自然-細(xì)胞生物學(xué)》Nature Cell Biology發(fā)表了來自上海市腫瘤研究所/上海交通大學(xué)腫瘤研究所癌基因及相關(guān)基因國家重點(diǎn)實(shí)驗(yàn)室研究人員獲得了microRNA與肝癌轉(zhuǎn)移的最新研究成果,。
MicroRNA是一類21~25個(gè)堿基的小分子非編碼RNA,，存在于各種真核生物中。MicroRNA主要通過促進(jìn)靶mRNA的降解或抑制其翻譯過程而發(fā)揮調(diào)控作用,，廣泛參與細(xì)胞增殖,、凋亡,、代謝及分化等過程,。MicroRNA的異常表達(dá)與腫瘤的發(fā)生,、發(fā)展及演進(jìn)有著極為密切的關(guān)系?；蚪M不穩(wěn)定性是惡性腫瘤的基本特征，在癌發(fā)生發(fā)展過程中經(jīng)常伴隨染色體的擴(kuò)增或缺失,，從而導(dǎo)致癌基因的激活或抑癌基因的失活,。許多microRNA分子定位于癌染色體變異區(qū)內(nèi)，可作為癌基因或抑癌基因而在癌變過程中發(fā)揮重要作用,。
該研究中,，作者在肝癌染色體變異區(qū)內(nèi)鑒定了肝癌轉(zhuǎn)移促進(jìn)因子miR-151，發(fā)現(xiàn)染色體8q24.3位點(diǎn)的擴(kuò)增導(dǎo)致了miR-151及其宿主基因FAK在肝癌中的高表達(dá),；miR-151過表達(dá)顯著增加肝癌細(xì)胞的遷移與侵襲能力,，并促進(jìn)肝癌細(xì)胞發(fā)生肝內(nèi)轉(zhuǎn)移；鑒定出RhoGDIA是miR-151下游靶基因,，介導(dǎo)miR-151的促肝癌轉(zhuǎn)移功能,；發(fā)現(xiàn)miR-151與宿主基因FAK協(xié)同作用活化Rac, cdc42及Rho GTPase，進(jìn)而促進(jìn)肝癌細(xì)胞的遷移、侵襲與轉(zhuǎn)移,。研究組通過利用antagomir（由廣州市銳博生物科技有限公司合成）抑制miRNA的表達(dá),，從而使腫瘤細(xì)胞轉(zhuǎn)移得到抑制。(生物谷Bioon.com)
生物谷推薦原文出處：
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.
