Oncotarget

Research Papers:

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 and Jong Hoon Park _

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Oncotarget. 2016; 7:55677-55689. https://doi.org/10.18632/oncotarget.10972

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Abstract

Hyun Kyung Kong1, Sae Jeong Park1, Ye Sol Kim1, Kyoung Min Kim2, Hyun-Woo Lee3,4, Hyeok-Gu Kang3,5, Yu Mi Woo1, Eun Young Park1, Je Yeong Ko1, Hiromu Suzuki6, Kyung-Hee Chun3,5, Erwei Song7, Kyu Yun Jang2, Jong Hoon Park1

1Department of Biological Science, Sookmyung Women’s University, Seoul, Republic of Korea

2Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea

3Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea

4Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea

5Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea

6Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan

7Department of Breast Surgery, Sun Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou, Peoples Republic of China

Correspondence to:

Jong Hoon Park, email: parkjh@sookmyung.ac.kr

Kyu Yun Jang, email: kyjang@chonbuk.ac.kr

Erwei Song, email: songerwei02@yahoo.com.cn

Keywords: breast cancer, LY6K, metastasis, DNA methylation, histone modification

Received: December 06, 2015    Accepted: July 06, 2016    Published: August 01, 2016

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.


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