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MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer

BACKGROUND: Side population (SP) cells and their relationship to stem cell-like properties have been insufficiently studied in colorectal cancer (CRC). MicroRNAs (miRNAs) have attracted much attention but their roles in the maintenance of SP phenotype remain unclear. METHODS: The SPs from CRC cell l...

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Autores principales: Xu, X T, Xu, Q, Tong, J L, Zhu, M M, Nie, F, Chen, X, Xiao, S D, Ran, Z H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314795/
https://www.ncbi.nlm.nih.gov/pubmed/22453125
http://dx.doi.org/10.1038/bjc.2012.88
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author Xu, X T
Xu, Q
Tong, J L
Zhu, M M
Nie, F
Chen, X
Xiao, S D
Ran, Z H
author_facet Xu, X T
Xu, Q
Tong, J L
Zhu, M M
Nie, F
Chen, X
Xiao, S D
Ran, Z H
author_sort Xu, X T
collection PubMed
description BACKGROUND: Side population (SP) cells and their relationship to stem cell-like properties have been insufficiently studied in colorectal cancer (CRC). MicroRNAs (miRNAs) have attracted much attention but their roles in the maintenance of SP phenotype remain unclear. METHODS: The SPs from CRC cell lines and primary cell cultures were analysed for stem cell-like properties. MiRNA microarray analysis identified miR-328 as a potential stemness miRNA of SP phenotype. The level of miR-328 expression in clinical samples and its correlation with SP fraction were determined. Gain-of-function and loss-of-function studies were performed to examine its roles in cancer stem-like SP cells. Furthermore, bioinformatics prediction and experimental validation were used to identify miR-328 target genes. RESULTS: The SP cells sorted from CRC possess cancer stem cell (CSC)-like properties, including self-renewal, differentiation, resistance to chemotherapy, invasive and strong tumour formation ability. MiR-328 expression was significantly reduced in SP cells compared with Non-SP cells (P<0.05). Moreover, miR-328 expression was downregulated in CRC (n=33, P<0.05) and low miR-328 expression tend to correlate with high SP fraction (n=15, r=0.6559, P<0.05, Pearson's correlation). Functional studies indicated that miR-328 expression affects the number of SP cells. In addition, miR-328 overexpression reversed drug resistance and inhibited cell invasion of SP cells. Furthermore, luciferase reporter assay demonstrated that miR-328 directly targets ABCG2 and MMP16 and affects the levels of mRNA and protein expression in SP cells. CONCLUSION: These findings indicate that CRC contain cancer stem-like SP cells. MiR-328 has an important role in maintaining cancer stem-like SP phenotype that may be a potential target for effective CRC therapy.
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spelling pubmed-33147952013-03-27 MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer Xu, X T Xu, Q Tong, J L Zhu, M M Nie, F Chen, X Xiao, S D Ran, Z H Br J Cancer Molecular Diagnostics BACKGROUND: Side population (SP) cells and their relationship to stem cell-like properties have been insufficiently studied in colorectal cancer (CRC). MicroRNAs (miRNAs) have attracted much attention but their roles in the maintenance of SP phenotype remain unclear. METHODS: The SPs from CRC cell lines and primary cell cultures were analysed for stem cell-like properties. MiRNA microarray analysis identified miR-328 as a potential stemness miRNA of SP phenotype. The level of miR-328 expression in clinical samples and its correlation with SP fraction were determined. Gain-of-function and loss-of-function studies were performed to examine its roles in cancer stem-like SP cells. Furthermore, bioinformatics prediction and experimental validation were used to identify miR-328 target genes. RESULTS: The SP cells sorted from CRC possess cancer stem cell (CSC)-like properties, including self-renewal, differentiation, resistance to chemotherapy, invasive and strong tumour formation ability. MiR-328 expression was significantly reduced in SP cells compared with Non-SP cells (P<0.05). Moreover, miR-328 expression was downregulated in CRC (n=33, P<0.05) and low miR-328 expression tend to correlate with high SP fraction (n=15, r=0.6559, P<0.05, Pearson's correlation). Functional studies indicated that miR-328 expression affects the number of SP cells. In addition, miR-328 overexpression reversed drug resistance and inhibited cell invasion of SP cells. Furthermore, luciferase reporter assay demonstrated that miR-328 directly targets ABCG2 and MMP16 and affects the levels of mRNA and protein expression in SP cells. CONCLUSION: These findings indicate that CRC contain cancer stem-like SP cells. MiR-328 has an important role in maintaining cancer stem-like SP phenotype that may be a potential target for effective CRC therapy. Nature Publishing Group 2012-03-27 2012-03-27 /pmc/articles/PMC3314795/ /pubmed/22453125 http://dx.doi.org/10.1038/bjc.2012.88 Text en Copyright © 2012 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular Diagnostics
Xu, X T
Xu, Q
Tong, J L
Zhu, M M
Nie, F
Chen, X
Xiao, S D
Ran, Z H
MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer
title MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer
title_full MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer
title_fullStr MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer
title_full_unstemmed MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer
title_short MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer
title_sort microrna expression profiling identifies mir-328 regulates cancer stem cell-like sp cells in colorectal cancer
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314795/
https://www.ncbi.nlm.nih.gov/pubmed/22453125
http://dx.doi.org/10.1038/bjc.2012.88
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