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

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...

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Autores principales: Kong, Hyun Kyung, Park, Sae Jeong, Kim, Ye Sol, Kim, Kyoung Min, Lee, Hyun-Woo, Kang, Hyeok-Gu, Woo, Yu Mi, Park, Eun Young, Ko, Je Yeong, Suzuki, Hiromu, Chun, Kyung-Hee, Song, Erwei, Jang, Kyu Yun, Park, Jong Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342445/
https://www.ncbi.nlm.nih.gov/pubmed/27494879
http://dx.doi.org/10.18632/oncotarget.10972
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author Kong, Hyun Kyung
Park, Sae Jeong
Kim, Ye Sol
Kim, Kyoung Min
Lee, Hyun-Woo
Kang, Hyeok-Gu
Woo, Yu Mi
Park, Eun Young
Ko, Je Yeong
Suzuki, Hiromu
Chun, Kyung-Hee
Song, Erwei
Jang, Kyu Yun
Park, Jong Hoon
author_facet Kong, Hyun Kyung
Park, Sae Jeong
Kim, Ye Sol
Kim, Kyoung Min
Lee, Hyun-Woo
Kang, Hyeok-Gu
Woo, Yu Mi
Park, Eun Young
Ko, Je Yeong
Suzuki, Hiromu
Chun, Kyung-Hee
Song, Erwei
Jang, Kyu Yun
Park, Jong Hoon
author_sort Kong, Hyun Kyung
collection PubMed
description 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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spelling pubmed-53424452017-03-22 Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma Kong, Hyun Kyung Park, Sae Jeong Kim, Ye Sol Kim, Kyoung Min Lee, Hyun-Woo Kang, Hyeok-Gu Woo, Yu Mi Park, Eun Young Ko, Je Yeong Suzuki, Hiromu Chun, Kyung-Hee Song, Erwei Jang, Kyu Yun Park, Jong Hoon Oncotarget Research Paper 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. Impact Journals LLC 2016-08-01 /pmc/articles/PMC5342445/ /pubmed/27494879 http://dx.doi.org/10.18632/oncotarget.10972 Text en Copyright: © 2016 Kong et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Kong, Hyun Kyung
Park, Sae Jeong
Kim, Ye Sol
Kim, Kyoung Min
Lee, Hyun-Woo
Kang, Hyeok-Gu
Woo, Yu Mi
Park, Eun Young
Ko, Je Yeong
Suzuki, Hiromu
Chun, Kyung-Hee
Song, Erwei
Jang, Kyu Yun
Park, Jong Hoon
Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma
title Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma
title_full Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma
title_fullStr Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma
title_full_unstemmed Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma
title_short Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma
title_sort epigenetic activation of ly6k predicts the presence of metastasis and poor prognosis in breast carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342445/
https://www.ncbi.nlm.nih.gov/pubmed/27494879
http://dx.doi.org/10.18632/oncotarget.10972
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