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FOXA1 Suppresses the Growth, Migration, and Invasion of Nasopharyngeal Carcinoma Cells through Repressing miR-100-5p and miR-125b-5p
Background: Nasopharyngeal carcinoma (NPC) is a unique subtype of head and neck cancer, within highest incidence in South China and southeastern Asia but rare in other regions worldwide. FOXA1 is a pioneer factor implicated in various human malignancies. Downregulation of FOXA1 promotes NPC cells pr...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066028/ https://www.ncbi.nlm.nih.gov/pubmed/32201519 http://dx.doi.org/10.7150/jca.40709 |
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author | Peng, Qian Zhang, Liyang Li, Junjun Wang, Wei Cai, Jing Ban, Yuanyuan Zhou, Ying Hu, Meng Mei, Yan Zeng, Zhaoyang Li, Xiaoling Xiong, Wei Li, Guiyuan Tan, Yixin Xiang, Bo Yi, Mei |
author_facet | Peng, Qian Zhang, Liyang Li, Junjun Wang, Wei Cai, Jing Ban, Yuanyuan Zhou, Ying Hu, Meng Mei, Yan Zeng, Zhaoyang Li, Xiaoling Xiong, Wei Li, Guiyuan Tan, Yixin Xiang, Bo Yi, Mei |
author_sort | Peng, Qian |
collection | PubMed |
description | Background: Nasopharyngeal carcinoma (NPC) is a unique subtype of head and neck cancer, within highest incidence in South China and southeastern Asia but rare in other regions worldwide. FOXA1 is a pioneer factor implicated in various human malignancies. Downregulation of FOXA1 promotes NPC cells proliferation, invasiveness in vitro and tumorigenicity in vivo. However, it is remain elusive to determine whether microRNAs (miRNAs) regulated by FOXA1 contribute to NPC progression. Methods: In this study, differentially expressed miRNAs and mRNAs induced by FOXA1 expression were determined by microarray. Integrative miRNA-mRNA regulatory networks mediated by FOXA1 in NPC were established. The expressions of differentially expressed miRNAs in NPC cells were measured by quantitative reverse-transcription PCR. Cell viability was determined by CCK-8 assays. Cell migration and invasiveness were measured by Transwell assays. The correlation between miRNAs and its target mRNAs was analyzed. Results: FOXA1 suppressed the expression of miR-100-5p and miR-125b-5p in NPC cells. Silencing either miR-100-5p or miR-125b-5p inhibited the malignant behaviors of NPC cells, whereas re-expression of miR-100-5p or miR-125b-5p restored the malignancy of NPC cells repressed by FOXA1. Mechanistically, miR-100-5p or miR-125b-5p suppressed RASGRP3 or FOXN3 expression respectively via direct binding to its 3'-UTR. Furthermore, we demonstrated that FOXA1 induced RASGRP3 or FOXN3 expression via inhibiting miR-100-5p or miR-125b-5p. Upregulation of RASGRP3 or FOXN3 contributed to inhibition of NPC by FOXA1. We also demonstrated that the mRNA levels of RASGRP3 and FOXN3 are positively correlated with FOXA1. Conclusion: Our study provided evidence the first time that FOXA1 suppresses NPC cells via downregulation of miR-100-5p or miR-125b-5p. |
format | Online Article Text |
id | pubmed-7066028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-70660282020-03-20 FOXA1 Suppresses the Growth, Migration, and Invasion of Nasopharyngeal Carcinoma Cells through Repressing miR-100-5p and miR-125b-5p Peng, Qian Zhang, Liyang Li, Junjun Wang, Wei Cai, Jing Ban, Yuanyuan Zhou, Ying Hu, Meng Mei, Yan Zeng, Zhaoyang Li, Xiaoling Xiong, Wei Li, Guiyuan Tan, Yixin Xiang, Bo Yi, Mei J Cancer Research Paper Background: Nasopharyngeal carcinoma (NPC) is a unique subtype of head and neck cancer, within highest incidence in South China and southeastern Asia but rare in other regions worldwide. FOXA1 is a pioneer factor implicated in various human malignancies. Downregulation of FOXA1 promotes NPC cells proliferation, invasiveness in vitro and tumorigenicity in vivo. However, it is remain elusive to determine whether microRNAs (miRNAs) regulated by FOXA1 contribute to NPC progression. Methods: In this study, differentially expressed miRNAs and mRNAs induced by FOXA1 expression were determined by microarray. Integrative miRNA-mRNA regulatory networks mediated by FOXA1 in NPC were established. The expressions of differentially expressed miRNAs in NPC cells were measured by quantitative reverse-transcription PCR. Cell viability was determined by CCK-8 assays. Cell migration and invasiveness were measured by Transwell assays. The correlation between miRNAs and its target mRNAs was analyzed. Results: FOXA1 suppressed the expression of miR-100-5p and miR-125b-5p in NPC cells. Silencing either miR-100-5p or miR-125b-5p inhibited the malignant behaviors of NPC cells, whereas re-expression of miR-100-5p or miR-125b-5p restored the malignancy of NPC cells repressed by FOXA1. Mechanistically, miR-100-5p or miR-125b-5p suppressed RASGRP3 or FOXN3 expression respectively via direct binding to its 3'-UTR. Furthermore, we demonstrated that FOXA1 induced RASGRP3 or FOXN3 expression via inhibiting miR-100-5p or miR-125b-5p. Upregulation of RASGRP3 or FOXN3 contributed to inhibition of NPC by FOXA1. We also demonstrated that the mRNA levels of RASGRP3 and FOXN3 are positively correlated with FOXA1. Conclusion: Our study provided evidence the first time that FOXA1 suppresses NPC cells via downregulation of miR-100-5p or miR-125b-5p. Ivyspring International Publisher 2020-02-10 /pmc/articles/PMC7066028/ /pubmed/32201519 http://dx.doi.org/10.7150/jca.40709 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Peng, Qian Zhang, Liyang Li, Junjun Wang, Wei Cai, Jing Ban, Yuanyuan Zhou, Ying Hu, Meng Mei, Yan Zeng, Zhaoyang Li, Xiaoling Xiong, Wei Li, Guiyuan Tan, Yixin Xiang, Bo Yi, Mei FOXA1 Suppresses the Growth, Migration, and Invasion of Nasopharyngeal Carcinoma Cells through Repressing miR-100-5p and miR-125b-5p |
title | FOXA1 Suppresses the Growth, Migration, and Invasion of Nasopharyngeal Carcinoma Cells through Repressing miR-100-5p and miR-125b-5p |
title_full | FOXA1 Suppresses the Growth, Migration, and Invasion of Nasopharyngeal Carcinoma Cells through Repressing miR-100-5p and miR-125b-5p |
title_fullStr | FOXA1 Suppresses the Growth, Migration, and Invasion of Nasopharyngeal Carcinoma Cells through Repressing miR-100-5p and miR-125b-5p |
title_full_unstemmed | FOXA1 Suppresses the Growth, Migration, and Invasion of Nasopharyngeal Carcinoma Cells through Repressing miR-100-5p and miR-125b-5p |
title_short | FOXA1 Suppresses the Growth, Migration, and Invasion of Nasopharyngeal Carcinoma Cells through Repressing miR-100-5p and miR-125b-5p |
title_sort | foxa1 suppresses the growth, migration, and invasion of nasopharyngeal carcinoma cells through repressing mir-100-5p and mir-125b-5p |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066028/ https://www.ncbi.nlm.nih.gov/pubmed/32201519 http://dx.doi.org/10.7150/jca.40709 |
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