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Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer

One reason for lack of efficacy in cancer therapeutics is tumor heterogeneity. We hypothesize that tumor heterogeneity arises due to emergence of multiple cancer stem cell (CSC) subpopulations because miRNAs regulate expression of stem cell genes in CSCs. Our goal was to determine if: i) multiple CS...

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Autores principales: Stark, Victoria A., Facey, Caroline O. B., Opdenaker, Lynn, Fields, Jeremy Z., Boman, Bruce M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934564/
https://www.ncbi.nlm.nih.gov/pubmed/36798319
http://dx.doi.org/10.1101/2023.02.06.527341
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author Stark, Victoria A.
Facey, Caroline O. B.
Opdenaker, Lynn
Fields, Jeremy Z.
Boman, Bruce M.
author_facet Stark, Victoria A.
Facey, Caroline O. B.
Opdenaker, Lynn
Fields, Jeremy Z.
Boman, Bruce M.
author_sort Stark, Victoria A.
collection PubMed
description One reason for lack of efficacy in cancer therapeutics is tumor heterogeneity. We hypothesize that tumor heterogeneity arises due to emergence of multiple cancer stem cell (CSC) subpopulations because miRNAs regulate expression of stem cell genes in CSCs. Our goal was to determine if: i) multiple CSC subpopulations exist in a human CRC cell population, and ii) miRNAs are differentially expressed in the different CSC subpopulations. We discovered that at least four different CSC populations (ALDH1, CD166, LGR5, LRIG1) exist in the HT29 cell line. CSC subpopulations were quantified using co-staining for multiple stem cell markers, isolated using FACS, and analyzed by NanoString miRNA profiling. The miRNA expression pattern in each CSC subpopulation was analyzed relative to miRNA expression patterns in other CSC subpopulations. Messenger RNAs predicted to be targeted by the upregulated miRNAs in each CSC subpopulation were: 1) identified using bioinformatics analyses, and 2) classified according to their predicted functions using David functional annotation analyses. We found multiple CSC subpopulations with a unique miRNA signature in each CSC subpopulation. Notably, the miRNAs expressed within one CSC subpopulation are predicted to target and downregulate the CSC genes and pathways that establish the other CSC subpopulations. Moreover, mRNAs predicted to be targeted by miRNAs in the different CSC subpopulations have different cellular functional classifications. That different CSC subpopulations express miRNAs that are predicted to target CSC genes expressed in other CSC subpopulations provides a mechanism that might explain the co-existence of multiple CSC subpopulations, tumor heterogeneity, and cancer therapy resistance.
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spelling pubmed-99345642023-02-17 Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer Stark, Victoria A. Facey, Caroline O. B. Opdenaker, Lynn Fields, Jeremy Z. Boman, Bruce M. bioRxiv Article One reason for lack of efficacy in cancer therapeutics is tumor heterogeneity. We hypothesize that tumor heterogeneity arises due to emergence of multiple cancer stem cell (CSC) subpopulations because miRNAs regulate expression of stem cell genes in CSCs. Our goal was to determine if: i) multiple CSC subpopulations exist in a human CRC cell population, and ii) miRNAs are differentially expressed in the different CSC subpopulations. We discovered that at least four different CSC populations (ALDH1, CD166, LGR5, LRIG1) exist in the HT29 cell line. CSC subpopulations were quantified using co-staining for multiple stem cell markers, isolated using FACS, and analyzed by NanoString miRNA profiling. The miRNA expression pattern in each CSC subpopulation was analyzed relative to miRNA expression patterns in other CSC subpopulations. Messenger RNAs predicted to be targeted by the upregulated miRNAs in each CSC subpopulation were: 1) identified using bioinformatics analyses, and 2) classified according to their predicted functions using David functional annotation analyses. We found multiple CSC subpopulations with a unique miRNA signature in each CSC subpopulation. Notably, the miRNAs expressed within one CSC subpopulation are predicted to target and downregulate the CSC genes and pathways that establish the other CSC subpopulations. Moreover, mRNAs predicted to be targeted by miRNAs in the different CSC subpopulations have different cellular functional classifications. That different CSC subpopulations express miRNAs that are predicted to target CSC genes expressed in other CSC subpopulations provides a mechanism that might explain the co-existence of multiple CSC subpopulations, tumor heterogeneity, and cancer therapy resistance. Cold Spring Harbor Laboratory 2023-02-06 /pmc/articles/PMC9934564/ /pubmed/36798319 http://dx.doi.org/10.1101/2023.02.06.527341 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Stark, Victoria A.
Facey, Caroline O. B.
Opdenaker, Lynn
Fields, Jeremy Z.
Boman, Bruce M.
Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer
title Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer
title_full Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer
title_fullStr Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer
title_full_unstemmed Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer
title_short Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer
title_sort differential mirna expression contributes to emergence of multiple cancer stem cell subpopulations in human colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934564/
https://www.ncbi.nlm.nih.gov/pubmed/36798319
http://dx.doi.org/10.1101/2023.02.06.527341
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