分析腫瘤細胞中微小核醣核酸的調控機制

Abstract

微小核醣核酸(microRNA/miRNA)是一段長度約為22核苷酸的非編碼的寡核醣核酸分子，它們主要功能是藉由抑制轉譯或是降解mRNA來降低基因的表現。近年來發現微小核醣核酸調控許多的基因與細胞功能有關，造成細胞凋亡，分化和發育。許多研究顯示出人類腫瘤形成(oncogenesis)與異常的微小核醣核酸表現量有關，但是大多數的調控機制仍有待發覺。在這篇研究中，我們分析了人類兩百多種在癌細胞中表現異常的微小核醣核酸，並測量其組織特異性,定義出20種在腫瘤形成中扮演重要角色的微小核醣核酸。這些微小核醣核酸分別在八種不同的癌細胞中扮演致癌基因或抑癌基因，藉由大量表現或不表現來調控下游的基因達到致癌目的。從計算不同癌細胞的基因表現與序列分析中，我們預測哪些轉錄因子會調控微小核醣核酸的表達，以及這些微小核醣核酸的標靶基因是否參與腫瘤形成。我們將分析結果建構出八種癌症疾病中微小核醣核酸和基因之間的調控網路，希望可以作為癌症研究或臨床實驗的參考。

MicroRNAs (miRNAs) are small non-coding RNA molecules of ~22 nt sequences that have an important role in the translational inhibition and degradation of mRNA to downregulate gene expression. Recent work supports miRNAs downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Recent studies have suggested that oncogenesis may be link with aberrant expression of miRNAs, but in most case it is still not clear what mechanism of miRNA leads to cancer formation. In this study, we analyzed more than 200 miRNAs which are aberrantly expressed in tumor cells, and the tissue specificity is tested by the miRNA expression among normal tissues. We identified 20 oncomirs which are up or down-expressed to regulate downstream genes and involved in oncogenesis of eight cancer types. We also predicted the transcription factor binding sites (TFBS) in miRNA promoter and identified miRNA targets which are tumour suppressors or oncogenes. Those analyses are integrated for miRNA regulatory network construction in eight cancers, and we hope our achievements can support cancer research and clinical trial.