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Long intergenic non-protein-coding RNA 1567 (LINC01567) acts as a “sponge” against microRNA-93 in regulating the proliferation and tumorigenesis of human colon cancer stem cells
BACKGROUND: Cancer stem cells (CSCs) are considered to be the major factor in tumor initiation, progression, metastasis, recurrence and chemoresistance. Maintaining the stemness and promoting differentiation of these cells involve various factors. Recently, long non-coding RNAs (lncRNAs) have been i...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674857/ https://www.ncbi.nlm.nih.gov/pubmed/29110645 http://dx.doi.org/10.1186/s12885-017-3731-5 |
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author | Yu, Xiaofeng Mi, Lin Dong, Jie Zou, Jian |
author_facet | Yu, Xiaofeng Mi, Lin Dong, Jie Zou, Jian |
author_sort | Yu, Xiaofeng |
collection | PubMed |
description | BACKGROUND: Cancer stem cells (CSCs) are considered to be the major factor in tumor initiation, progression, metastasis, recurrence and chemoresistance. Maintaining the stemness and promoting differentiation of these cells involve various factors. Recently, long non-coding RNAs (lncRNAs) have been identified as new regulatory factors in human cancer cells. However, the function of lncRNAs in colon CSCs is still unknown. METHODS: Primary colon cancer cells were maintained in serum-free medium to form spheres and CD133(+)/CD166(+)/CD44(+) spheroid cells were selected using FACS technique. Then we detected growth curve, colony formation, invasion and migration ability, and tumorigenicity of CD133(+)/CD166(+)/CD44(+) cells. LOCCS-siRNA and pcDNA-LOCCS plasmid vectors were constructed and transfected to evaluate impact of the lncRNA. We also performed dual luciferase reporter assay to verify the interaction of LOCCS and miR-93. RESULTS: The research explored lncRNA expression and the regulatory role of novel lncRNAs in colon CSCs. Using the stem cell markers CD133, CD166 and CD44, we found a subpopulation of highly tumorigenic human colon cancer cells. They displayed some characteristics of stem cells, including the ability to proliferate and form colonies, to resist chemotherapeutic drugs, and to produce xenografts in nude mice. We also found an lncRNA, LOCCS, with obviously upregulated expression in colon CSCs. Knockdown of LOCCS reduced cell proliferation, invasion, migration, and generation of tumor xenografts. Furthermore, microRNA-93 (miR-93) and Musashi-1 mediated the tumor suppression of LOCCS knockdown. CONCLUSIONS: There was reciprocal repression between LOCCS and miR-93. Research on mechanisms suggested direct binding, as a predicted miR-93 binding site was identified in LOCCS. This comprehensive analysis of LOCCS in colon CSCs provides insight for elucidating important roles of the lncRNA–microRNA functional network in human colon cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3731-5) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5674857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-56748572017-11-15 Long intergenic non-protein-coding RNA 1567 (LINC01567) acts as a “sponge” against microRNA-93 in regulating the proliferation and tumorigenesis of human colon cancer stem cells Yu, Xiaofeng Mi, Lin Dong, Jie Zou, Jian BMC Cancer Research Article BACKGROUND: Cancer stem cells (CSCs) are considered to be the major factor in tumor initiation, progression, metastasis, recurrence and chemoresistance. Maintaining the stemness and promoting differentiation of these cells involve various factors. Recently, long non-coding RNAs (lncRNAs) have been identified as new regulatory factors in human cancer cells. However, the function of lncRNAs in colon CSCs is still unknown. METHODS: Primary colon cancer cells were maintained in serum-free medium to form spheres and CD133(+)/CD166(+)/CD44(+) spheroid cells were selected using FACS technique. Then we detected growth curve, colony formation, invasion and migration ability, and tumorigenicity of CD133(+)/CD166(+)/CD44(+) cells. LOCCS-siRNA and pcDNA-LOCCS plasmid vectors were constructed and transfected to evaluate impact of the lncRNA. We also performed dual luciferase reporter assay to verify the interaction of LOCCS and miR-93. RESULTS: The research explored lncRNA expression and the regulatory role of novel lncRNAs in colon CSCs. Using the stem cell markers CD133, CD166 and CD44, we found a subpopulation of highly tumorigenic human colon cancer cells. They displayed some characteristics of stem cells, including the ability to proliferate and form colonies, to resist chemotherapeutic drugs, and to produce xenografts in nude mice. We also found an lncRNA, LOCCS, with obviously upregulated expression in colon CSCs. Knockdown of LOCCS reduced cell proliferation, invasion, migration, and generation of tumor xenografts. Furthermore, microRNA-93 (miR-93) and Musashi-1 mediated the tumor suppression of LOCCS knockdown. CONCLUSIONS: There was reciprocal repression between LOCCS and miR-93. Research on mechanisms suggested direct binding, as a predicted miR-93 binding site was identified in LOCCS. This comprehensive analysis of LOCCS in colon CSCs provides insight for elucidating important roles of the lncRNA–microRNA functional network in human colon cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3731-5) contains supplementary material, which is available to authorized users. BioMed Central 2017-11-06 /pmc/articles/PMC5674857/ /pubmed/29110645 http://dx.doi.org/10.1186/s12885-017-3731-5 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Yu, Xiaofeng Mi, Lin Dong, Jie Zou, Jian Long intergenic non-protein-coding RNA 1567 (LINC01567) acts as a “sponge” against microRNA-93 in regulating the proliferation and tumorigenesis of human colon cancer stem cells |
title | Long intergenic non-protein-coding RNA 1567 (LINC01567) acts as a “sponge” against microRNA-93 in regulating the proliferation and tumorigenesis of human colon cancer stem cells |
title_full | Long intergenic non-protein-coding RNA 1567 (LINC01567) acts as a “sponge” against microRNA-93 in regulating the proliferation and tumorigenesis of human colon cancer stem cells |
title_fullStr | Long intergenic non-protein-coding RNA 1567 (LINC01567) acts as a “sponge” against microRNA-93 in regulating the proliferation and tumorigenesis of human colon cancer stem cells |
title_full_unstemmed | Long intergenic non-protein-coding RNA 1567 (LINC01567) acts as a “sponge” against microRNA-93 in regulating the proliferation and tumorigenesis of human colon cancer stem cells |
title_short | Long intergenic non-protein-coding RNA 1567 (LINC01567) acts as a “sponge” against microRNA-93 in regulating the proliferation and tumorigenesis of human colon cancer stem cells |
title_sort | long intergenic non-protein-coding rna 1567 (linc01567) acts as a “sponge” against microrna-93 in regulating the proliferation and tumorigenesis of human colon cancer stem cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674857/ https://www.ncbi.nlm.nih.gov/pubmed/29110645 http://dx.doi.org/10.1186/s12885-017-3731-5 |
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