组蛋白变体H1.4调控非小细胞肺癌EMT过程的作用机制

作为连接组蛋白H1家族成员之一，组蛋白变体H1.4在异染色质形成、细胞周期及肿瘤发生等方面起着重要的作用。然而，H1.4在非小细胞肺癌中的作用，特别是在非小细胞肺癌上皮间质转化(EMT)中的作用，目前尚不了解。最近我们的预实验结果显示，H1.4的表达通过诱导E-cadherin启动子的甲基化抑制了E-cadherin的表达，以及H1.4的乙酰化修饰参与了N-cadherin表达的调控过程。此外，我们的结果表明，H1.4的shRNA敲低显著地抑制了A549细胞的生长和迁移等。因此，我们的数据提示了H1.4可能参与了非小细胞肺癌EMT过程的调控。本研究将探索H1.4的表达及其乙酰化修饰在非小细胞肺癌EMT过程中的作用，并鉴定EMT过程中H1.4调控的基因。本项目是一个创新的科研计划，将为进一步阐明非小细胞肺癌EMT的调控机制奠定基础。

As a member of linker histone H1 family, histone variant H1.4 plays important roles in heterochromatin formation, cell cycle and tumorigenesis, etc. However, little is known about the roles of H1.4 in non-small cell lung cancer (NSCLC), especially in the epithelial-mesenchymal transition (EMT) of NSCLC. Recently, our preliminary data showed that over-expression of H1.4 inhibited the expression of E-cadherin by inducing methylation of E-cadherin promoter, and acetylation modification of H1.4 was involved in regulation of N-cadherin expression. Moreover, our results indicated that depletion of H1.4 by shRNA knockdown significantly inhibited growth and migration of A549 cells. Therefore, our data suggested that H1.4 was probably involved in the regulation of EMT process in NSCLC cells. In this study, we will explore the roles of H1.4 expression and its acetylation modification in the EMT process of NSCLC, and identify the genes regulated by H1.4 during EMT process. This project is an innovative research plan that would pave the way for elucidating the regulatory mechanism of EMT in NSCLC cells.