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KMT2A histone methyltransferase contributes to colorectal cancer development by promoting cathepsin Z transcriptional activation

Accumulating evidence supports the notion that epigenetic modifiers are abnormal in carcinogenesis and have a fundamental role in cancer progression. Among these aberrant epigenetic modifiers, the function of histone methyltransferase KMT2A in somatic tumors is not well known. By analyzing KMT2A exp...

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Autores principales: Fang, Yang, Zhang, Dan, Hu, Tingting, Zhao, Hongyan, Zhao, Xuan, Lou, Zhefeng, He, Yongshan, Qin, Wenzheng, Xia, Jianfu, Zhang, Xiaohua, Ye, Le‐chi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601586/
https://www.ncbi.nlm.nih.gov/pubmed/31090199
http://dx.doi.org/10.1002/cam4.2226
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author Fang, Yang
Zhang, Dan
Hu, Tingting
Zhao, Hongyan
Zhao, Xuan
Lou, Zhefeng
He, Yongshan
Qin, Wenzheng
Xia, Jianfu
Zhang, Xiaohua
Ye, Le‐chi
author_facet Fang, Yang
Zhang, Dan
Hu, Tingting
Zhao, Hongyan
Zhao, Xuan
Lou, Zhefeng
He, Yongshan
Qin, Wenzheng
Xia, Jianfu
Zhang, Xiaohua
Ye, Le‐chi
author_sort Fang, Yang
collection PubMed
description Accumulating evidence supports the notion that epigenetic modifiers are abnormal in carcinogenesis and have a fundamental role in cancer progression. Among these aberrant epigenetic modifiers, the function of histone methyltransferase KMT2A in somatic tumors is not well known. By analyzing KMT2A expression in patient tissues, we demonstrated that KMT2A was overexpressed in colorectal cancer tissues in comparison with adjacent normal tissues and its expression was positively correlated with cancer stages. In KMT2A‐knockdown HCT116 and DLD1 cells, cell invasion and migration were consequently suppressed. In addition, KMT2A depletion effectively suppressed cancer metastasis in vivo. Mechanistically, cathepsin Z (CTSZ) was demonstrated to be an important downstream gene of KMT2A. Further studies showed that p65 could recruit KMT2A on the promoter region of the downstream gene CTSZ and knockdown of p65 could reduce the KMT2A on the promoter of CTSZ. Finally, our present study revealed that KMT2A epigenetically promotes cancer progression by targeting CTSZ, which has specific functions in cancer invasion and metastasis.
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spelling pubmed-66015862019-07-22 KMT2A histone methyltransferase contributes to colorectal cancer development by promoting cathepsin Z transcriptional activation Fang, Yang Zhang, Dan Hu, Tingting Zhao, Hongyan Zhao, Xuan Lou, Zhefeng He, Yongshan Qin, Wenzheng Xia, Jianfu Zhang, Xiaohua Ye, Le‐chi Cancer Med Cancer Biology Accumulating evidence supports the notion that epigenetic modifiers are abnormal in carcinogenesis and have a fundamental role in cancer progression. Among these aberrant epigenetic modifiers, the function of histone methyltransferase KMT2A in somatic tumors is not well known. By analyzing KMT2A expression in patient tissues, we demonstrated that KMT2A was overexpressed in colorectal cancer tissues in comparison with adjacent normal tissues and its expression was positively correlated with cancer stages. In KMT2A‐knockdown HCT116 and DLD1 cells, cell invasion and migration were consequently suppressed. In addition, KMT2A depletion effectively suppressed cancer metastasis in vivo. Mechanistically, cathepsin Z (CTSZ) was demonstrated to be an important downstream gene of KMT2A. Further studies showed that p65 could recruit KMT2A on the promoter region of the downstream gene CTSZ and knockdown of p65 could reduce the KMT2A on the promoter of CTSZ. Finally, our present study revealed that KMT2A epigenetically promotes cancer progression by targeting CTSZ, which has specific functions in cancer invasion and metastasis. John Wiley and Sons Inc. 2019-05-15 /pmc/articles/PMC6601586/ /pubmed/31090199 http://dx.doi.org/10.1002/cam4.2226 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Fang, Yang
Zhang, Dan
Hu, Tingting
Zhao, Hongyan
Zhao, Xuan
Lou, Zhefeng
He, Yongshan
Qin, Wenzheng
Xia, Jianfu
Zhang, Xiaohua
Ye, Le‐chi
KMT2A histone methyltransferase contributes to colorectal cancer development by promoting cathepsin Z transcriptional activation
title KMT2A histone methyltransferase contributes to colorectal cancer development by promoting cathepsin Z transcriptional activation
title_full KMT2A histone methyltransferase contributes to colorectal cancer development by promoting cathepsin Z transcriptional activation
title_fullStr KMT2A histone methyltransferase contributes to colorectal cancer development by promoting cathepsin Z transcriptional activation
title_full_unstemmed KMT2A histone methyltransferase contributes to colorectal cancer development by promoting cathepsin Z transcriptional activation
title_short KMT2A histone methyltransferase contributes to colorectal cancer development by promoting cathepsin Z transcriptional activation
title_sort kmt2a histone methyltransferase contributes to colorectal cancer development by promoting cathepsin z transcriptional activation
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601586/
https://www.ncbi.nlm.nih.gov/pubmed/31090199
http://dx.doi.org/10.1002/cam4.2226
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