甲基化介导的胞外基质蛋白Dermatopontin基因沉默促进肝癌的侵袭转移

肝癌是我国发病率和死亡率最高的恶性肿瘤之一，而侵袭转移是肝癌致死的主要原因。因此，加深对肝癌转移机制的了解，对于改善肝癌的诊治水平起着至关重要的作用。细胞外基质蛋白是肿瘤微环境的主要成员，在肝癌发生、发展和转移的过程中发挥着关键作用。尽管目前已发现了一些影响肝癌转移的细胞外基质蛋白，但大多数细胞外基质蛋白成员对肝癌转移及其它方面的影响还有待研究。我们初步研究发现，细胞外基质蛋白Dermatopontin(DPT)在肝癌组织中的表达显著降低，其表达水平与肝癌侵袭转移以及病人预后密切相关。然后，我们又发现DPT在肝癌中的低表达是由于DNA甲基化所造成；过表达DPT能够显著抑制肝癌细胞生长和侵袭转移。本研究将进一步深入研究DPT在肝癌中的表达调控机制及其抑制肝癌生长和侵袭转移的分子机制。

Hepatocellular carcinoma (HCC) is one of the most fatal disease in China. Cancer metastasis is the main cause of death from HCC. Therefore, understanding the mechanisms of HCC metastasis is of great importance in improving the diagnosis and treatment of HCC. Extracellular matrix (ECM) proteins are main components of the tumor microenvironment and play fundamental roles in HCC initiation, progression and metastasis. Currently, some ECM proteins have been proved to function on HCC metastasis, but the effects of the majority of ECM proteins in HCC metastasis are not studied yet. ECM protein dermatopontin (DPT) is a secreted protein with a molecular weight of 22KD. It has been reported that DPT plays crucial roles in mediating the cross talk between parenchymal cells in microenvironment, but its roles in HCC has not been studied yet. Our preliminary studies revealed that DPT expression was significantly decreased in HCC tissue compared to paracancerous tissue, and the expression level of DPT is related to the overall survival rate and relapse-free survival rate of HCC patients. Afterwards, we found that low expression of DPT in HCC was induced by DNA methylation and overexpression of DPT significantly inhibited the growth and metastasis of HCC in vivo and in vitro. In this study, we will go further to reveal how DPT expression is modulated by epigenetic factors and the mechanisms of DPT in regulating HCC growth and metastasis.