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miR-19a targets CLCA4 to regulate the proliferation, migration, and invasion of colorectal cancer cells

The role of miR-19a in colorectal cancer (CRC), a devastating disease with high mortality and morbidity, remains controversial. In the present study, we show that the level of miR-19a is significantly higher in clinical CRC tissue samples than in paracancerous tissue samples, and significantly highe...

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Autores principales: Li, Huiwen, Huang, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PAGEPress Publications, Pavia, Italy 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958453/
https://www.ncbi.nlm.nih.gov/pubmed/35266369
http://dx.doi.org/10.4081/ejh.2022.3381
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author Li, Huiwen
Huang, Bo
author_facet Li, Huiwen
Huang, Bo
author_sort Li, Huiwen
collection PubMed
description The role of miR-19a in colorectal cancer (CRC), a devastating disease with high mortality and morbidity, remains controversial. In the present study, we show that the level of miR-19a is significantly higher in clinical CRC tissue samples than in paracancerous tissue samples, and significantly higher in CRC cells lines HT29, SW480, and CaCO2 than in the normal human colon mucosal epithelial cell line NCM460. miR-19a mimics and inhibitors were synthesized and validated. Overexpression of miR-19a mimics significantly promoted, while miR-19a inhibitors inhibited, the proliferation, survival, migration, and invasion of SW480 and CaCO2 CRC cells. Furthermore, mRNA and protein levels of chloride channel accessory 4 (CLCA4) were lower in CRC cells and tissues. Bioinformatics and a luciferase reporter assay confirmed that CLCA4 was a miR-19a target. Further, miR-19a inhibition increased CLCA4 expression. The inhibitory effect of miR-19a on cell growth, survival, migration, and invasion was reversed by knockdown of CLCA4 expression. The data demonstrated that the miR-19a/CLCA4 axis modulates phospho-activation of the PI3K/AKT pathway in CRC cells. In conclusion, our results revealed that miR-19a overexpression decreases CLCA4 levels to promote CRC oncogenesis, suggesting that miR-19a inhibitors have potential applications for future therapeutic of CRC.
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spelling pubmed-89584532022-03-29 miR-19a targets CLCA4 to regulate the proliferation, migration, and invasion of colorectal cancer cells Li, Huiwen Huang, Bo Eur J Histochem Article The role of miR-19a in colorectal cancer (CRC), a devastating disease with high mortality and morbidity, remains controversial. In the present study, we show that the level of miR-19a is significantly higher in clinical CRC tissue samples than in paracancerous tissue samples, and significantly higher in CRC cells lines HT29, SW480, and CaCO2 than in the normal human colon mucosal epithelial cell line NCM460. miR-19a mimics and inhibitors were synthesized and validated. Overexpression of miR-19a mimics significantly promoted, while miR-19a inhibitors inhibited, the proliferation, survival, migration, and invasion of SW480 and CaCO2 CRC cells. Furthermore, mRNA and protein levels of chloride channel accessory 4 (CLCA4) were lower in CRC cells and tissues. Bioinformatics and a luciferase reporter assay confirmed that CLCA4 was a miR-19a target. Further, miR-19a inhibition increased CLCA4 expression. The inhibitory effect of miR-19a on cell growth, survival, migration, and invasion was reversed by knockdown of CLCA4 expression. The data demonstrated that the miR-19a/CLCA4 axis modulates phospho-activation of the PI3K/AKT pathway in CRC cells. In conclusion, our results revealed that miR-19a overexpression decreases CLCA4 levels to promote CRC oncogenesis, suggesting that miR-19a inhibitors have potential applications for future therapeutic of CRC. PAGEPress Publications, Pavia, Italy 2022-03-10 /pmc/articles/PMC8958453/ /pubmed/35266369 http://dx.doi.org/10.4081/ejh.2022.3381 Text en ©Copyright: the Author(s) https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Li, Huiwen
Huang, Bo
miR-19a targets CLCA4 to regulate the proliferation, migration, and invasion of colorectal cancer cells
title miR-19a targets CLCA4 to regulate the proliferation, migration, and invasion of colorectal cancer cells
title_full miR-19a targets CLCA4 to regulate the proliferation, migration, and invasion of colorectal cancer cells
title_fullStr miR-19a targets CLCA4 to regulate the proliferation, migration, and invasion of colorectal cancer cells
title_full_unstemmed miR-19a targets CLCA4 to regulate the proliferation, migration, and invasion of colorectal cancer cells
title_short miR-19a targets CLCA4 to regulate the proliferation, migration, and invasion of colorectal cancer cells
title_sort mir-19a targets clca4 to regulate the proliferation, migration, and invasion of colorectal cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958453/
https://www.ncbi.nlm.nih.gov/pubmed/35266369
http://dx.doi.org/10.4081/ejh.2022.3381
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