Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma.
Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma.
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DOI：
10.18632/oncotarget.10972
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发表时间：
2016-08-23
期刊：
影响因子：
--
通讯作者：
Park JH
中科院分区：
文献类型：
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作者：
Kong HK;Park SJ;Kim YS;Kim KM;Lee HW;Kang HG;Woo YM;Park EY;Ko JY;Suzuki H;Chun KH;Song E;Jang KY;Park JH
淋巴细胞抗原 6 复合体 K 位点 (LY6K) 在乳腺癌中的作用已被研究，但 LY6K 转录的表观遗传控制尚不完全清楚。在此，我们通过多变量分析报告，LY6K 表达升高的乳腺癌患者比 LY6K 水平低的患者无病生存期和总生存期更短。与没有远处转移的乳腺癌患者相比，LY6K 在有远处转移的乳腺癌患者中表达上调，从而下调 E-钙粘蛋白的表达。此外，LY6K 敲低裸鼠的异种移植肿瘤体积比用对照慢病毒治疗的小鼠减少。有趣的是，LY6K 在转录起始位点周围有一个 CpG 岛 (CGI)，而在其启动子中则有一个非 CGI，称为 CGI 岸。 LY6K 表达不仅与 CGI 中的甲基化呈负相关，而且与 CGI shore 中的甲基化呈负相关，后者与组蛋白修饰相关。此外，由于 LY6K CGI shore 中的 SNP242 突变，PAX3 转录因子增加了 LY6K 甲基化。综上所述，乳腺癌风险和转移不仅与 LY6K 表达显着相关，还与 SNP242 突变诱导的 CGI shore 甲基化显着相关。我们的结果表明，了解 LY6K 基因的表观遗传机制可能有助于诊断转移性乳腺癌患者的致癌风险和预测结果。
The role of lymphocyte antigen 6 complex, locus K (LY6K) in breast cancer has been studied, whereas the epigenetic control of LY6K transcription is not fully understood. Here, we report that breast cancer patients with increased LY6K expression had shorter disease-free and overall survival than the patients with low levels of LY6K by multivariate analysis. LY6K also was upregulated in breast cancer patients with distant metastases than those without distant metastases, downregulating E-cadherin expression. Furthermore, xenograft tumor volumes from LY6K knockdown nude mice were reduced than those of mice treated with control lentivirus. Interestingly, LY6K has a CpG island (CGI) around the transcription start site and non-CGI in its promoter, called a CGI shore. LY6K expression was inversely correlated with methylation in not only CGI but CGI shore, which are associated with histone modifications. Additionally, LY6K methylation was increased by the PAX3 transcription factor due to the SNP242 mutation in LY6K CGI shore. Taken together, breast cancer risk and metastasis were significantly associated with not only LY6K expression, but also methylation of CGI shore which induced by SNP242 mutation. Our results suggest that an understanding epigenetic mechanism of the LY6K gene may be useful to diagnose carcinogenic risk and predict outcomes of patients with metastatic breast cancer.