| Abstract: | 本計畫主要是探討微型核糖核酸(miRNA)扮演致癌及抑癌基因的角式。透過整合不同類型之資料，即miRNA標靶資料(TarBase)、miRNA及mRNA表達資料(NCI60)、癌症基因微晶片資料(ArrayExpress, SMD)、miRNA標靶預測工具(miRanda, RNAHybrid)、基因功能註解資料庫(Gene Ontology)及文獻資料(PubMed)等，探討miRNA扮演此調控的角式。
我們將進一步整合miRNA、miRNA標靶基因、siRNA、siRNA標靶基因，蛋白質相互作用及OMIM之資料，建立miRNA及siRNA與疾病相關的調控路徑。此外也開發工具探討與癌症相關的miRNA基因叢集，預測與癌症相關的短小核糖核酸。最後我們也將針對第一及第二年的研究結果建置網站提供查詢服務。
另一方面此計畫結合生物資訊研究人員(主持人)及生物醫學研究人員(共同主持人)之經驗，將生物資訊預測的結果經由生物實驗驗証miRNA 是否扮演致癌及抑癌的角式。生物實驗驗証部份擬分兩年執行，我們將依序完成四個主要的研究目標︰1. 確認預測的miRNAs及其標靶mRNAs在細胞中的表現相關性。2. 合成miRNA抑制物，抑制此miRNA之表現，觀察其是否可以影響相關抑癌/致癌基因的表現。3. 確認此預測的miRNA在mRNA上的target site。4. 研究此miRNA對癌細胞的生長速率、anchorage independence 或apoptosis的影響，及其背後的分子機轉。
The main purpose of this proposal is to establish the possibility that microRNA (miRNA) could play the role of an oncogene and tumor suppressor gene. By integrating heterogeneous types of data, that is miRNA targets (TarBase), miRNA and mRNA expression level data (NCI-60), cancer type microarray data (ArrayExpress, SMD), miRNA target prediction tools (miRanda, RNAHybrid), gene annotation database (Gene Ontology) and literatures data (PubMed), to investigate the relationship between miRNA and cancer.
Furthermore, in this proposal we will integrate miRNA, miRNA targets, siRNA, siRNA targets, protein-protein interactions and the OMIM data to reconstruct the miRNA and siRNA disease related pathways. Also, a miRNA gene cluster prediction tool will be developed to predict more cancer related miRNA genes. Year one and year two results will be deployed as an web service.
On the other hand, the PI and co-PI of this proposal will work together in order to valid the cancer related miRNA bioinformatics predictions by in vivo experiments. In this part, we will focus on four major goals, to be completed in two years time, which are outlined below: 1. To examine the expression profiles of miRNAs with those of their target genes’ mRNAs in vivo. 2. To validate the correlation between miRNA and its target gene via a reverse genetic tool, anti-miRNA inhibitor. 3. To examine the predicted target sites of cancer-related miRNAs. 4. To examine the mechanisms by which the predicted miRNAs effect on carcinogenesis in vivo, that is to examine the ability of miRNA to inhibit cancer cells growth, anchorage independence, apoptosis, and understand the underlying molecular mechanism. |
