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miRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer

Changes in miRNA expression are a common feature in colon cancer. Those changes occurring in the transition from normal to adenoma and from adenoma to carcinoma, however, have not been well defined. Additionally, miRNA changes among tumor subgroups of colon cancer have also not been adequately evalu...

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Autores principales: Oberg, Ann L., French, Amy J., Sarver, Aaron L., Subramanian, Subbaya, Morlan, Bruce W., Riska, Shaun M., Borralho, Pedro M., Cunningham, Julie M., Boardman, Lisa A., Wang, Liang, Smyrk, Thomas C., Asmann, Yan, Steer, Clifford J., Thibodeau, Stephen N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111419/
https://www.ncbi.nlm.nih.gov/pubmed/21694772
http://dx.doi.org/10.1371/journal.pone.0020465
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author Oberg, Ann L.
French, Amy J.
Sarver, Aaron L.
Subramanian, Subbaya
Morlan, Bruce W.
Riska, Shaun M.
Borralho, Pedro M.
Cunningham, Julie M.
Boardman, Lisa A.
Wang, Liang
Smyrk, Thomas C.
Asmann, Yan
Steer, Clifford J.
Thibodeau, Stephen N.
author_facet Oberg, Ann L.
French, Amy J.
Sarver, Aaron L.
Subramanian, Subbaya
Morlan, Bruce W.
Riska, Shaun M.
Borralho, Pedro M.
Cunningham, Julie M.
Boardman, Lisa A.
Wang, Liang
Smyrk, Thomas C.
Asmann, Yan
Steer, Clifford J.
Thibodeau, Stephen N.
author_sort Oberg, Ann L.
collection PubMed
description Changes in miRNA expression are a common feature in colon cancer. Those changes occurring in the transition from normal to adenoma and from adenoma to carcinoma, however, have not been well defined. Additionally, miRNA changes among tumor subgroups of colon cancer have also not been adequately evaluated. In this study, we examined the global miRNA expression in 315 samples that included 52 normal colonic mucosa, 41 tubulovillous adenomas, 158 adenocarcinomas with proficient DNA mismatch repair (pMMR) selected for stage and age of onset, and 64 adenocarcinomas with defective DNA mismatch repair (dMMR) selected for sporadic (n = 53) and inherited colon cancer (n = 11). Sporadic dMMR tumors all had MLH1 inactivation due to promoter hypermethylation. Unsupervised PCA and cluster analysis demonstrated that normal colon tissue, adenomas, pMMR carcinomas and dMMR carcinomas were all clearly discernable. The majority of miRNAs that were differentially expressed between normal and polyp were also differentially expressed with a similar magnitude in the comparison of normal to both the pMMR and dMMR tumor groups, suggesting a stepwise progression for transformation from normal colon to carcinoma. Among the miRNAs demonstrating the largest fold up- or down-regulated changes (≥4), four novel (miR-31, miR-1, miR-9 and miR-99a) and two previously reported (miR-137 and miR-135b) miRNAs were identified in the normal/adenoma comparison. All but one of these (miR-99a) demonstrated similar expression differences in the two normal/carcinoma comparisons, suggesting that these early tumor changes are important in both the pMMR- and dMMR-derived cancers. The comparison between pMMR and dMMR tumors identified four miRNAs (miR-31, miR-552, miR-592 and miR-224) with statistically significant expression differences (≥2-fold change).
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spelling pubmed-31114192011-06-21 miRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer Oberg, Ann L. French, Amy J. Sarver, Aaron L. Subramanian, Subbaya Morlan, Bruce W. Riska, Shaun M. Borralho, Pedro M. Cunningham, Julie M. Boardman, Lisa A. Wang, Liang Smyrk, Thomas C. Asmann, Yan Steer, Clifford J. Thibodeau, Stephen N. PLoS One Research Article Changes in miRNA expression are a common feature in colon cancer. Those changes occurring in the transition from normal to adenoma and from adenoma to carcinoma, however, have not been well defined. Additionally, miRNA changes among tumor subgroups of colon cancer have also not been adequately evaluated. In this study, we examined the global miRNA expression in 315 samples that included 52 normal colonic mucosa, 41 tubulovillous adenomas, 158 adenocarcinomas with proficient DNA mismatch repair (pMMR) selected for stage and age of onset, and 64 adenocarcinomas with defective DNA mismatch repair (dMMR) selected for sporadic (n = 53) and inherited colon cancer (n = 11). Sporadic dMMR tumors all had MLH1 inactivation due to promoter hypermethylation. Unsupervised PCA and cluster analysis demonstrated that normal colon tissue, adenomas, pMMR carcinomas and dMMR carcinomas were all clearly discernable. The majority of miRNAs that were differentially expressed between normal and polyp were also differentially expressed with a similar magnitude in the comparison of normal to both the pMMR and dMMR tumor groups, suggesting a stepwise progression for transformation from normal colon to carcinoma. Among the miRNAs demonstrating the largest fold up- or down-regulated changes (≥4), four novel (miR-31, miR-1, miR-9 and miR-99a) and two previously reported (miR-137 and miR-135b) miRNAs were identified in the normal/adenoma comparison. All but one of these (miR-99a) demonstrated similar expression differences in the two normal/carcinoma comparisons, suggesting that these early tumor changes are important in both the pMMR- and dMMR-derived cancers. The comparison between pMMR and dMMR tumors identified four miRNAs (miR-31, miR-552, miR-592 and miR-224) with statistically significant expression differences (≥2-fold change). Public Library of Science 2011-06-09 /pmc/articles/PMC3111419/ /pubmed/21694772 http://dx.doi.org/10.1371/journal.pone.0020465 Text en Oberg et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Oberg, Ann L.
French, Amy J.
Sarver, Aaron L.
Subramanian, Subbaya
Morlan, Bruce W.
Riska, Shaun M.
Borralho, Pedro M.
Cunningham, Julie M.
Boardman, Lisa A.
Wang, Liang
Smyrk, Thomas C.
Asmann, Yan
Steer, Clifford J.
Thibodeau, Stephen N.
miRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer
title miRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer
title_full miRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer
title_fullStr miRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer
title_full_unstemmed miRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer
title_short miRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer
title_sort mirna expression in colon polyps provides evidence for a multihit model of colon cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111419/
https://www.ncbi.nlm.nih.gov/pubmed/21694772
http://dx.doi.org/10.1371/journal.pone.0020465
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