摘要：RNA的剪接是調節基因功能的重要機制之一，近年來，mRNA的剪接在癌症 的重要性已逐漸被學者所重視，但在肝細胞癌的角色仍然不清楚。MBNL2是一 個mRNA剪接因子。它的失去功能是強直性肌肉失養症的重要機制，近來研究發 現它和胚胎幹細胞的分化有關。我們的初步研究發現，MBNL2在肝細胞癌過度 表現，在正常肝組織，MBNL2表現在膽管和肝臟幹細胞所在之處。在本研究中， 我們將探討MBNL2及其相關的剪接作用在肝細胞癌的角色。我們的目標包括：(一)決定MBNL2在肝細胞癌的表現頻率及其表現的臨床病理意義。(二）探討MBNL2在肝臟再生及肝臟幹細胞功能的角色。(三）決定MBNL2在腫瘤生成和侵犯的角色。(四）找出MBNL2所造成的mRNA剪接，並研究此剪接對基因功能的影響。
Abstract: RNA splicing is one of the major mechanisms in regulating gene function. Recently, the importance of RNA splicing in tumorigenesis are gradually recognized by researchers. However, the roles of RNA splicing in hepatocellular carcinoma (HCC) are still unknown. MBNL2 is an mRNA splicing factor. Loss of function of MBNL2 is a major mechanism for the pathogenesis of myotonic dystrophy. A recent study showed it plays important roles in the differentiation process of embryonic stem cell. Our preliminary data showed overexpression of MBNL2 in HCC. Besides, in normal liver tissue, MBNL2 is expression in the loci of hepatic stem cell. In this research, we will explore the role of MBNL2 and its associated RNA splicing pattern in the carcinogenesis of HCC. The specific aims are:1.Aim 1. To determine the expression frequency of MBNL2 in HCC and the clinicopathologic significance of MBNL2 expression in HCC.2.Aim 2. To explore the role of MBNL2 in liver regeneration and hepatic stem cell.3.Aim 3. To determine the roles of MBNL2 in the tumor formation and invasion of HCC.4.Aim 4. To identify the mRNA splicing pattern associated with MBNL2 and study the effect of splicing on gene function.