我们应用功能蛋白组学研究策略获得PRL-3功能相关蛋白（J Proteome Res，2010）,并发现PRL-3参与结肠癌细胞Histone H3 9 位赖氨酸去甲基化（Gut, 2012）。免疫共沉淀结果表明，Histone H3及USP4可能是PRL-3核内新型相互作用蛋白。基于此我们提出PRL-3 与Histone H3 的功能联系：介导Histone H3 修饰模式改变从而调控结直肠癌细胞生物学特性。本研究围绕Histone H3磷酸化修饰、甲基化修饰及泛素化等修饰模式的改变、基因表达模式变化与结直肠癌细胞生物学特性特别是增殖、侵袭和转移特性之间的联系；从Histone H3 的核定位、对HistoneH3 修饰及相关基因的转录调控的影响等方面确定PRL-3 调控结直肠细胞生物学特性的分子机制，并在结直肠癌的临床组织标本中进行验证，从而阐明PRL-3 调控结直肠癌表观遗传机制。

In our previous works, we have identified some PRL-3 functionally associated proteins using functional proteomic strategies(J Proteome Res, 2010).And, we found that PRL-3 is involved in regulating methylation of Histone H3K9 in colorectal cancer(CRC)(Gut,2012).Co-immunoprecipitation assay showed that Histone H3 and USP4 are the candidates of PRL-3 nuclear interacting proteins. Based on these findings, we suggest a functional association between PRL-3 and Histone H3 by regulating the modified patterns of Histone H3, which will result in behaviour changes of CRC cells. Here we will aim to study the relationship between modified patterns such as phosphorylation, methylation, acetylation or SUMOylation of Histone H3 triggered by PRL-3, gene expression patterns and behaviour changes in proliferation, invasion and metastasis of CRC cells. The roles of modified patterns of Histone induced by PRL-3 will also be confirmed in clinical samples of CRC and the potential clinical significance will also be determined. We will uncover a new epigenetic mechanism of PRL-3 involoved in CRC.