微型核醣核酸在乳癌所調控的蛋白質交互作用網路及其功能

MicroRNA-regulated protein-protein interaction networks and their functions in breast cancer

李佳憲(Chia-Hsien Lee)

指導教授 ： 阮雪芬

共同指導教授 ： 歐陽彥正(Yen-Jen Oyang)

國立臺灣大學/電機資訊學院/生醫電子與資訊學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.10911

摘要

微型核醣核酸是一種被發現和許多種的癌症有關連性的內生性基因調節分子。有些微型核醣核酸會調控和癌症功能相關的基因，包括細胞凋亡、細胞新生、抑制癌症或是導致癌症產生。乳癌對於全世界的女性而言是一個主要的健康威脅。有許多的微型核醣核酸被報導與乳癌的癌化及進程有關，本研究主要在探討並試圖尋找新的與乳癌相關的微型核醣核酸。
首先，我們把微型核醣核酸的目標預測資料庫與微型核糖核酸、訊息核糖核酸的表現資訊整合在一起，以找出具信心的微型核醣核酸─目標配對。由於我們把實際在乳癌與正常組織中的表現資訊考慮進去，我們得以降低偽陽性，並且取得與乳癌功能相關的微型核醣核酸─目標配對。接著，我們利用具信心的微型核醣核酸─目標配對，以及在HPRD中已知的蛋白質交互作用資料來建立微型核醣核酸與其調控的蛋白質交互作用網路。最後，我們利用功能性分析來找出微型核糖核酸與其調控的蛋白質交互作用網路所擁有的功能。
從我們的結果看來，我們除了找到了miR-125a、miR-125b、miR-21以及miR-497這些之前已知和乳癌相關的微型核糖核酸，也找到有些以前未曾報告過與乳癌相關的微型核糖核酸，例如miR-139和miR-383；同時，我們也試著在這篇研究中推測它們的功能。我們更利用其他表現量資料跑ROC曲線分析，使用GOBO做存活率分析，以及文獻搜尋來驗證我們的結果。我們的結果可能可以替未來的乳癌相關的微型核糖核酸的研究提供一些新的線索。

關鍵字

微型核醣核酸 ； 乳癌 ； 蛋白質交互作用網路 ； 功能性分析

並列摘要

MicroRNAs, small endogenous RNA regulators, were found to be related to various types of cancer. Some of the miRNAs which target some tumor related genes, including apoptosis and cell proliferation, were confirmed to be tumor suppressors or oncomirs. Breast cancer is a major health threat for women worldwide. Many miRNAs were reported to be associated to the progression and carcinogenesis of breast cancer. In this work, we tried to elucidate and discover novel breast cancer related miRNAs.
First, we find confident miRNA-target pairs by combining miRNA target prediction databases and expression profiles of miRNA and mRNA. By considering actual expression profiles in normal and breast tumor samples, we may reduce false positives while obtaining the miRNA-target pairs relevant to breast cancer. miRNA-regulated PINs were then constructed with the confident pairs and known interaction data in HPRD. Finally, the functions of miRNA-regulated PINs were then elucidated by functional enrichment analysis.
From the result, we found some previously known breast cancer-related miRNAs and functions of the PIN, like miR-125b, miR-125a, miR-21, and miR-497. Some miRNAs without known association to breast cancer were also found, and the putative functions of their PINs were also elucidated. Such novel miRNAs were miR-139 and miR-383. Furthermore, we tried to validate our result by ROC analysis using another expression profile data, GOBO survival analysis, and literature search. Our results may provide new insights for researches of breast cancer associated miRNAs.

並列關鍵字

miRNA ； breast cancer ； protein interaction network ； functional analysis

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