Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma

Hyun Kyung Kong, Sae Jeong Park, Ye Sol Kim, Kyoung Min Kim, Hyun Woo Lee, Hyeok Gu Kang, Yu Mi Woo, Eun Young Park, Je Yeong Ko, Hiromu Suzuki, Kyung Hee Chun, Erwei Song, Kyu Yun Jang, Jong Hoon Park

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)55677-55689
Number of pages13
JournalOncotarget
Volume7
Issue number34
DOIs
StatePublished - 2016

Keywords

  • Breast cancer
  • DNA methylation
  • Histone modification
  • LY6K
  • Metastasis

Fingerprint

Dive into the research topics of 'Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma'. Together they form a unique fingerprint.

Cite this