Molecular analysis of colorectal cancer with LINE-1 hypomethylation and its application to cancer diagnosis and therapy

我们研究了5-FU对LINE-1低甲基化肿瘤有效的机制。LINE-1表达状态与肿瘤对5-FU的敏感性无关。LINE-1低甲基化的肿瘤中染色质结构松散。染色质疏松的结直肠癌细胞对5-FU的敏感性高于染色质浓缩的结直肠癌细胞。结果表明，LINE-1低甲基化和染色质结构之间的关联是5-FU抗癌活性机制的基础。LINE-1表达的敲低导致癌症生长的抑制。许多抗癌药物抑制LINE-1的表达，提示抑制LINE-1可能是5-FU与其他抗癌药物协同作用的机制之一。这些发现对于实现个性化化疗和开发使用5-FU的新策略可能很重要。

We investigated the mechanism by which 5-FU is effective on the tumor with LINE-1 hypomethylation. LINE-1 expression status is not associated with tumor sensitivity to 5-FU. Chromatin structure looses in the tumor with LINE-1 hypomethylation. Colorectal cancer cell with loosed chromatin is more sensitive to 5-FU compared to one with condensed chromatin. The results suggest that the association between LINE-1 hypomethylation and chromatin structure underlies mechanism of anticancer activity of 5-FU. Knockdown of LINE-1 expression results in suppression of cancer growth. Many anticancer drugs inhibit LINE-1 expression, suggesting that suppression of LINE-1 might be one of mechanism by which 5-FU and other anticancer drugs shows synergistic effect. These findings could be important for achieving personalized chemotherapy and developing novel strategy using 5-FU.