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The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway
Polycomb group protein enhancer of zeste homolog 2 (EZH2) is a methyltransferase that correlates with the regulation of invasion and metastasis and is overexpressed in human cancers such as colorectal cancer. MicroRNA-31 (miR-31) plays an oncogenic role and is associated with BRAF mutation and poor...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914316/ https://www.ncbi.nlm.nih.gov/pubmed/26871294 http://dx.doi.org/10.18632/oncotarget.7260 |
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author | Kurihara, Hiroyoshi Maruyama, Reo Ishiguro, Kazuya Kanno, Shinichi Yamamoto, Itaru Ishigami, Keisuke Mitsuhashi, Kei Igarashi, Hisayoshi Ito, Miki Tanuma, Tokuma Sukawa, Yasutaka Okita, Kenji Hasegawa, Tadashi Imai, Kohzoh Yamamoto, Hiroyuki Shinomura, Yasuhisa Nosho, Katsuhiko |
author_facet | Kurihara, Hiroyoshi Maruyama, Reo Ishiguro, Kazuya Kanno, Shinichi Yamamoto, Itaru Ishigami, Keisuke Mitsuhashi, Kei Igarashi, Hisayoshi Ito, Miki Tanuma, Tokuma Sukawa, Yasutaka Okita, Kenji Hasegawa, Tadashi Imai, Kohzoh Yamamoto, Hiroyuki Shinomura, Yasuhisa Nosho, Katsuhiko |
author_sort | Kurihara, Hiroyoshi |
collection | PubMed |
description | Polycomb group protein enhancer of zeste homolog 2 (EZH2) is a methyltransferase that correlates with the regulation of invasion and metastasis and is overexpressed in human cancers such as colorectal cancer. MicroRNA-31 (miR-31) plays an oncogenic role and is associated with BRAF mutation and poor prognosis in colorectal cancer. EZH2 is functionally considered to suppress miR-31 expression in human cancers; however, no study has reported its relationship with colon cancer. We therefore evaluated EZH2 expression using immunohistochemistry and assessed miR-31 and epigenetic alterations using 301 colorectal carcinomas and 207 premalignant lesions. Functional analysis was performed to identify the association between EZH2 and miR-31 using cancer cell lines. In the current study, negative, weak, moderate, and strong EZH2 expressions were observed in 15%, 19%, 25%, and 41% of colorectal cancers, respectively. EZH2 was inversely associated with miR-31 (P < 0.0001), independent of clinicopathological and molecular features. In a multivariate stage-stratified analysis, high EZH2 expression was related to favorable prognosis (P = 0.0022). Regarding premalignant lesions, negative EZH2 expression was frequently detected in sessile serrated adenomas/polyps (SSA/Ps) (76%; P < 0.0001) compared with hyperplastic polyps, traditional serrated adenomas, and non-serrated adenomas (25–36%). Functional analysis demonstrated that the knockdown of EZH2 increased miR-31 expression. In conclusion, an inverse association was identified between EZH2 and miR-31 in colorectal cancers. Our data also showed that upregulation of EZH2 expression may be rare in SSA/Ps. These results suggest that EZH2 suppresses miR-31 in colorectal cancer and may correlate with differentiation and evolution of serrated pathway. |
format | Online Article Text |
id | pubmed-4914316 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-49143162016-07-11 The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway Kurihara, Hiroyoshi Maruyama, Reo Ishiguro, Kazuya Kanno, Shinichi Yamamoto, Itaru Ishigami, Keisuke Mitsuhashi, Kei Igarashi, Hisayoshi Ito, Miki Tanuma, Tokuma Sukawa, Yasutaka Okita, Kenji Hasegawa, Tadashi Imai, Kohzoh Yamamoto, Hiroyuki Shinomura, Yasuhisa Nosho, Katsuhiko Oncotarget Research Paper Polycomb group protein enhancer of zeste homolog 2 (EZH2) is a methyltransferase that correlates with the regulation of invasion and metastasis and is overexpressed in human cancers such as colorectal cancer. MicroRNA-31 (miR-31) plays an oncogenic role and is associated with BRAF mutation and poor prognosis in colorectal cancer. EZH2 is functionally considered to suppress miR-31 expression in human cancers; however, no study has reported its relationship with colon cancer. We therefore evaluated EZH2 expression using immunohistochemistry and assessed miR-31 and epigenetic alterations using 301 colorectal carcinomas and 207 premalignant lesions. Functional analysis was performed to identify the association between EZH2 and miR-31 using cancer cell lines. In the current study, negative, weak, moderate, and strong EZH2 expressions were observed in 15%, 19%, 25%, and 41% of colorectal cancers, respectively. EZH2 was inversely associated with miR-31 (P < 0.0001), independent of clinicopathological and molecular features. In a multivariate stage-stratified analysis, high EZH2 expression was related to favorable prognosis (P = 0.0022). Regarding premalignant lesions, negative EZH2 expression was frequently detected in sessile serrated adenomas/polyps (SSA/Ps) (76%; P < 0.0001) compared with hyperplastic polyps, traditional serrated adenomas, and non-serrated adenomas (25–36%). Functional analysis demonstrated that the knockdown of EZH2 increased miR-31 expression. In conclusion, an inverse association was identified between EZH2 and miR-31 in colorectal cancers. Our data also showed that upregulation of EZH2 expression may be rare in SSA/Ps. These results suggest that EZH2 suppresses miR-31 in colorectal cancer and may correlate with differentiation and evolution of serrated pathway. Impact Journals LLC 2016-02-08 /pmc/articles/PMC4914316/ /pubmed/26871294 http://dx.doi.org/10.18632/oncotarget.7260 Text en Copyright: © 2016 Kurihara 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 Kurihara, Hiroyoshi Maruyama, Reo Ishiguro, Kazuya Kanno, Shinichi Yamamoto, Itaru Ishigami, Keisuke Mitsuhashi, Kei Igarashi, Hisayoshi Ito, Miki Tanuma, Tokuma Sukawa, Yasutaka Okita, Kenji Hasegawa, Tadashi Imai, Kohzoh Yamamoto, Hiroyuki Shinomura, Yasuhisa Nosho, Katsuhiko The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway |
title | The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway |
title_full | The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway |
title_fullStr | The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway |
title_full_unstemmed | The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway |
title_short | The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway |
title_sort | relationship between ezh2 expression and microrna-31 in colorectal cancer and the role in evolution of the serrated pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914316/ https://www.ncbi.nlm.nih.gov/pubmed/26871294 http://dx.doi.org/10.18632/oncotarget.7260 |
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