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miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression

Background: Human N-acetyltransferase 10 (NAT10) plays pivotal roles in cellular biological processes, such as senescence, autophagy and cytokinesis. The expression of NAT10 is dysregulated in colorectal cancer (CRC) and is associated with the prognosis of patients. However, it remains unclear how N...

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Autores principales: Liu, Zhenzhen, Liu, Xiaofeng, Li, Yuan, Ren, Pengwei, Zhang, Chunfeng, Wang, Lijun, Du, Xiaojuan, Xing, Baocai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559146/
https://www.ncbi.nlm.nih.gov/pubmed/31239781
http://dx.doi.org/10.2147/CMAR.S197733
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author Liu, Zhenzhen
Liu, Xiaofeng
Li, Yuan
Ren, Pengwei
Zhang, Chunfeng
Wang, Lijun
Du, Xiaojuan
Xing, Baocai
author_facet Liu, Zhenzhen
Liu, Xiaofeng
Li, Yuan
Ren, Pengwei
Zhang, Chunfeng
Wang, Lijun
Du, Xiaojuan
Xing, Baocai
author_sort Liu, Zhenzhen
collection PubMed
description Background: Human N-acetyltransferase 10 (NAT10) plays pivotal roles in cellular biological processes, such as senescence, autophagy and cytokinesis. The expression of NAT10 is dysregulated in colorectal cancer (CRC) and is associated with the prognosis of patients. However, it remains unclear how NAT10 is regulated in CRC. Methods: The microRNA(miRNA) regulating NAT10 was predicted by bioinformatics analysis and further validated by real-time quantitative PCR(RT-qPCR),Western blot and dual luciferase reporter assays. The expression of the miRNA regulating NAT10 in CRC tissues was examined using RT-qPCR. Cell proliferation, cell apoptosis, cell migration and cell invasion assays were performed after transfection with miRNA mimic and inhibitor. Results: Here, we report that miR-6716-5p inhibits the expression of NAT10 in CRC. The NAT10 protein level was downregulated by the miR-6716-5p mimic, and was upregulated by the miR-6716-5p inhibitor in CRC cell lines. In addition, miR-6716-5p bound to the 3ʹ-untranslated region of NAT10 mRNA and decreased NAT10 mRNA levels. Significantly, the miR-6716-5p level was higher in the tumor tissues of the CRC patients with liver metastasis than that in the non-metastatic CRC patients. In addition, the miR-6716-5p level was correlated with poor overall survival of CRC patients with liver metastasis. The miR-6716-5p inhibitor inhibited CRC cell migration and invasion. Consistently, the miR-6716-5p mimic significantly promoted cell migration and invasion, and this effect is dependent on NAT10. However, miR-6716-5p had no effect on CRC cell proliferation and apoptosis. We found that miR-6716-5p negatively regulated E-cadherin protein levels. In addition, E-cadherin was upregulated by NAT10 in CRC cells, confirming that miR-6716-5p downregulated E-cadherin levels by inhibiting NAT10 expression. Conclusion: We demonstrated that miR-6716-5p acts as a crucial regulator of NAT10 to promote cell migration and invasion in CRC by inhibiting NAT10 expression. Our data suggest that miR-6716-5p/NAT10 might act as a potential therapeutic target for CRC treatment.
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spelling pubmed-65591462019-06-25 miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression Liu, Zhenzhen Liu, Xiaofeng Li, Yuan Ren, Pengwei Zhang, Chunfeng Wang, Lijun Du, Xiaojuan Xing, Baocai Cancer Manag Res Original Research Background: Human N-acetyltransferase 10 (NAT10) plays pivotal roles in cellular biological processes, such as senescence, autophagy and cytokinesis. The expression of NAT10 is dysregulated in colorectal cancer (CRC) and is associated with the prognosis of patients. However, it remains unclear how NAT10 is regulated in CRC. Methods: The microRNA(miRNA) regulating NAT10 was predicted by bioinformatics analysis and further validated by real-time quantitative PCR(RT-qPCR),Western blot and dual luciferase reporter assays. The expression of the miRNA regulating NAT10 in CRC tissues was examined using RT-qPCR. Cell proliferation, cell apoptosis, cell migration and cell invasion assays were performed after transfection with miRNA mimic and inhibitor. Results: Here, we report that miR-6716-5p inhibits the expression of NAT10 in CRC. The NAT10 protein level was downregulated by the miR-6716-5p mimic, and was upregulated by the miR-6716-5p inhibitor in CRC cell lines. In addition, miR-6716-5p bound to the 3ʹ-untranslated region of NAT10 mRNA and decreased NAT10 mRNA levels. Significantly, the miR-6716-5p level was higher in the tumor tissues of the CRC patients with liver metastasis than that in the non-metastatic CRC patients. In addition, the miR-6716-5p level was correlated with poor overall survival of CRC patients with liver metastasis. The miR-6716-5p inhibitor inhibited CRC cell migration and invasion. Consistently, the miR-6716-5p mimic significantly promoted cell migration and invasion, and this effect is dependent on NAT10. However, miR-6716-5p had no effect on CRC cell proliferation and apoptosis. We found that miR-6716-5p negatively regulated E-cadherin protein levels. In addition, E-cadherin was upregulated by NAT10 in CRC cells, confirming that miR-6716-5p downregulated E-cadherin levels by inhibiting NAT10 expression. Conclusion: We demonstrated that miR-6716-5p acts as a crucial regulator of NAT10 to promote cell migration and invasion in CRC by inhibiting NAT10 expression. Our data suggest that miR-6716-5p/NAT10 might act as a potential therapeutic target for CRC treatment. Dove 2019-06-06 /pmc/articles/PMC6559146/ /pubmed/31239781 http://dx.doi.org/10.2147/CMAR.S197733 Text en © 2019 Liu et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Liu, Zhenzhen
Liu, Xiaofeng
Li, Yuan
Ren, Pengwei
Zhang, Chunfeng
Wang, Lijun
Du, Xiaojuan
Xing, Baocai
miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression
title miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression
title_full miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression
title_fullStr miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression
title_full_unstemmed miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression
title_short miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression
title_sort mir-6716-5p promotes metastasis of colorectal cancer through downregulating nat10 expression
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559146/
https://www.ncbi.nlm.nih.gov/pubmed/31239781
http://dx.doi.org/10.2147/CMAR.S197733
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