PCDH18 is frequently inactivated by promoter methylation in colorectal cancer

Abstract Protocadherin18 (PCDH18) was found to be preferentially methylated and inactivated in colorectal cancer (CRC) using bioinformatics tools. However, its biologic role in tumorgenesis remains unclear. Herein, we aimed to elucidate its epigenetic regulation and biological functions in CRC. The...

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Autores principales:	Dan Zhou, Weiwei Tang, Guoqiang Su, Mingquan Cai, Han-Xiang An, Yun Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/86ea3e61d1f44fe1b263cc2f241253d6
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spelling	oai:doaj.org-article:86ea3e61d1f44fe1b263cc2f241253d62021-12-02T16:06:55ZPCDH18 is frequently inactivated by promoter methylation in colorectal cancer10.1038/s41598-017-03133-w2045-2322https://doaj.org/article/86ea3e61d1f44fe1b263cc2f241253d62017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03133-whttps://doaj.org/toc/2045-2322Abstract Protocadherin18 (PCDH18) was found to be preferentially methylated and inactivated in colorectal cancer (CRC) using bioinformatics tools. However, its biologic role in tumorgenesis remains unclear. Herein, we aimed to elucidate its epigenetic regulation and biological functions in CRC. The methylation status of PCDH18 was significant higher in CRC tissues than in adjacent non-tumor tissues (median, 15.17% vs. median, 0.4438%). Expression level of PCDH18 was significantly lower in primary CRCs than in nonmalignant tissues. Importantly, methylation status of PCDH18 in cell-free DNA of CRC patients was also significantly higher than in healthy subjects. PCDH18 was readily expressed in NCM460 cells, but downregulated in 100% (4/4) of CRC cell lines by promoter methylation, despite its expression could be restored through demethylation treatment. Overexpression of PCDH18 suppressed CRC cell viability, colony formation and migration. Meanwhile, the depletion of PCDH18 by siRNA in NCM460 cells enhanced the colonogenicity and migration ability and promoted β-catenin nuclear accumulation, whereas it inhibited cell cycle arrest. These effects were associated with upregulation of phospho-GSK-3β and cyclin D1, and downregulation of caspase3 and p21. Our results suggested that PCDH18 was a putative tumor suppressor with epigenetic silencing in CRC and a potential biomarker for CRC diagnosis.Dan ZhouWeiwei TangGuoqiang SuMingquan CaiHan-Xiang AnYun ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dan Zhou Weiwei Tang Guoqiang Su Mingquan Cai Han-Xiang An Yun Zhang PCDH18 is frequently inactivated by promoter methylation in colorectal cancer
description	Abstract Protocadherin18 (PCDH18) was found to be preferentially methylated and inactivated in colorectal cancer (CRC) using bioinformatics tools. However, its biologic role in tumorgenesis remains unclear. Herein, we aimed to elucidate its epigenetic regulation and biological functions in CRC. The methylation status of PCDH18 was significant higher in CRC tissues than in adjacent non-tumor tissues (median, 15.17% vs. median, 0.4438%). Expression level of PCDH18 was significantly lower in primary CRCs than in nonmalignant tissues. Importantly, methylation status of PCDH18 in cell-free DNA of CRC patients was also significantly higher than in healthy subjects. PCDH18 was readily expressed in NCM460 cells, but downregulated in 100% (4/4) of CRC cell lines by promoter methylation, despite its expression could be restored through demethylation treatment. Overexpression of PCDH18 suppressed CRC cell viability, colony formation and migration. Meanwhile, the depletion of PCDH18 by siRNA in NCM460 cells enhanced the colonogenicity and migration ability and promoted β-catenin nuclear accumulation, whereas it inhibited cell cycle arrest. These effects were associated with upregulation of phospho-GSK-3β and cyclin D1, and downregulation of caspase3 and p21. Our results suggested that PCDH18 was a putative tumor suppressor with epigenetic silencing in CRC and a potential biomarker for CRC diagnosis.
format	article
author	Dan Zhou Weiwei Tang Guoqiang Su Mingquan Cai Han-Xiang An Yun Zhang
author_facet	Dan Zhou Weiwei Tang Guoqiang Su Mingquan Cai Han-Xiang An Yun Zhang
author_sort	Dan Zhou
title	PCDH18 is frequently inactivated by promoter methylation in colorectal cancer
title_short	PCDH18 is frequently inactivated by promoter methylation in colorectal cancer
title_full	PCDH18 is frequently inactivated by promoter methylation in colorectal cancer
title_fullStr	PCDH18 is frequently inactivated by promoter methylation in colorectal cancer
title_full_unstemmed	PCDH18 is frequently inactivated by promoter methylation in colorectal cancer
title_sort	pcdh18 is frequently inactivated by promoter methylation in colorectal cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/86ea3e61d1f44fe1b263cc2f241253d6
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_version_	1718384788076756992

PCDH18 is frequently inactivated by promoter methylation in colorectal cancer

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