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KMT5A promotes metastasis of clear cell renal cell carcinoma through reducing cadherin-1 expression

Clear cell renal cell carcinoma (ccRCC) is one of the most common types of kidney cancer and is accompanied by a poor prognosis due to a high potential for metastasis and recurrence. The mechanism of ccRCC metastasis is not well known. N-lysine methyltransferase KMT5A serves a crucial role in the pr...

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Autores principales: Lin, Zhen-Zhong, Ming, De-Song, Chen, Ya-Bin, Zhang, Jian-Ming, Chen, Hui-Hua, Jiang, Jian-Jia, Zhang, Zhi-Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507477/
https://www.ncbi.nlm.nih.gov/pubmed/31186699
http://dx.doi.org/10.3892/ol.2019.10163
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author Lin, Zhen-Zhong
Ming, De-Song
Chen, Ya-Bin
Zhang, Jian-Ming
Chen, Hui-Hua
Jiang, Jian-Jia
Zhang, Zhi-Shan
author_facet Lin, Zhen-Zhong
Ming, De-Song
Chen, Ya-Bin
Zhang, Jian-Ming
Chen, Hui-Hua
Jiang, Jian-Jia
Zhang, Zhi-Shan
author_sort Lin, Zhen-Zhong
collection PubMed
description Clear cell renal cell carcinoma (ccRCC) is one of the most common types of kidney cancer and is accompanied by a poor prognosis due to a high potential for metastasis and recurrence. The mechanism of ccRCC metastasis is not well known. N-lysine methyltransferase KMT5A serves a crucial role in the progression of human cancer; however, the function of KMT5A in the development of ccRCCs has not yet been investigated, which has triggered an interest in investigating the potential association between KMT5A and ccRCC. The present study demonstrates for the first time that KMT5A is a driving factor in ccRCC metastasis. The KMT5A expression level was revealed to be significantly higher in ccRCC tissues compared with adjacent normal tissues. Patients with ccRCC whose tumors expressed high levels of KMT5A were demonstrated to have significantly shorter postoperative survival times. In vitro knockdown of KMT5A expression in 786-O cells inhibited cell migration and invasion. KMT5A reduced cadherin-1 (CDH1) protein levels by directly inhibiting its transcription. The CDH1 mRNA levels were inversely correlated with KMT5A expression in ccRCC samples. Patients with high tumor KMT5A or low CDH1 levels had the poorest prognosis with the shortest overall survival (OS) time, and this combination was demonstrated to be an independent prognostic indicator for patient OS time in ccRCC, more accurate than monitoring KMT5A or CDH1 alone. Together, these results indicate that KMT5A serves a vital role in ccRCC development and progression, and it may be a novel target for ccRCC treatment and prevention.
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spelling pubmed-65074772019-06-11 KMT5A promotes metastasis of clear cell renal cell carcinoma through reducing cadherin-1 expression Lin, Zhen-Zhong Ming, De-Song Chen, Ya-Bin Zhang, Jian-Ming Chen, Hui-Hua Jiang, Jian-Jia Zhang, Zhi-Shan Oncol Lett Articles Clear cell renal cell carcinoma (ccRCC) is one of the most common types of kidney cancer and is accompanied by a poor prognosis due to a high potential for metastasis and recurrence. The mechanism of ccRCC metastasis is not well known. N-lysine methyltransferase KMT5A serves a crucial role in the progression of human cancer; however, the function of KMT5A in the development of ccRCCs has not yet been investigated, which has triggered an interest in investigating the potential association between KMT5A and ccRCC. The present study demonstrates for the first time that KMT5A is a driving factor in ccRCC metastasis. The KMT5A expression level was revealed to be significantly higher in ccRCC tissues compared with adjacent normal tissues. Patients with ccRCC whose tumors expressed high levels of KMT5A were demonstrated to have significantly shorter postoperative survival times. In vitro knockdown of KMT5A expression in 786-O cells inhibited cell migration and invasion. KMT5A reduced cadherin-1 (CDH1) protein levels by directly inhibiting its transcription. The CDH1 mRNA levels were inversely correlated with KMT5A expression in ccRCC samples. Patients with high tumor KMT5A or low CDH1 levels had the poorest prognosis with the shortest overall survival (OS) time, and this combination was demonstrated to be an independent prognostic indicator for patient OS time in ccRCC, more accurate than monitoring KMT5A or CDH1 alone. Together, these results indicate that KMT5A serves a vital role in ccRCC development and progression, and it may be a novel target for ccRCC treatment and prevention. D.A. Spandidos 2019-06 2019-03-19 /pmc/articles/PMC6507477/ /pubmed/31186699 http://dx.doi.org/10.3892/ol.2019.10163 Text en Copyright: © Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Lin, Zhen-Zhong
Ming, De-Song
Chen, Ya-Bin
Zhang, Jian-Ming
Chen, Hui-Hua
Jiang, Jian-Jia
Zhang, Zhi-Shan
KMT5A promotes metastasis of clear cell renal cell carcinoma through reducing cadherin-1 expression
title KMT5A promotes metastasis of clear cell renal cell carcinoma through reducing cadherin-1 expression
title_full KMT5A promotes metastasis of clear cell renal cell carcinoma through reducing cadherin-1 expression
title_fullStr KMT5A promotes metastasis of clear cell renal cell carcinoma through reducing cadherin-1 expression
title_full_unstemmed KMT5A promotes metastasis of clear cell renal cell carcinoma through reducing cadherin-1 expression
title_short KMT5A promotes metastasis of clear cell renal cell carcinoma through reducing cadherin-1 expression
title_sort kmt5a promotes metastasis of clear cell renal cell carcinoma through reducing cadherin-1 expression
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507477/
https://www.ncbi.nlm.nih.gov/pubmed/31186699
http://dx.doi.org/10.3892/ol.2019.10163
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