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Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding

BACKGROUND: MiRNAs are often deregulated in colorectal cancer and might function as tumor suppressors or as oncogenes. They participate in controlling key signaling pathways involved in proliferation, invasion and apoptosis and may serve as prognostic and predictive markers. In this study we aimed t...

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Autores principales: Baltruskeviciene, Edita, Schveigert, Diana, Stankevicius, Vaidotas, Mickys, Ugnius, Zvirblis, Tadas, Bublevic, Jaroslav, Suziedelis, Kestutis, Aleknavicius, Eduardas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580437/
https://www.ncbi.nlm.nih.gov/pubmed/28863773
http://dx.doi.org/10.1186/s12885-017-3575-z
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author Baltruskeviciene, Edita
Schveigert, Diana
Stankevicius, Vaidotas
Mickys, Ugnius
Zvirblis, Tadas
Bublevic, Jaroslav
Suziedelis, Kestutis
Aleknavicius, Eduardas
author_facet Baltruskeviciene, Edita
Schveigert, Diana
Stankevicius, Vaidotas
Mickys, Ugnius
Zvirblis, Tadas
Bublevic, Jaroslav
Suziedelis, Kestutis
Aleknavicius, Eduardas
author_sort Baltruskeviciene, Edita
collection PubMed
description BACKGROUND: MiRNAs are often deregulated in colorectal cancer and might function as tumor suppressors or as oncogenes. They participate in controlling key signaling pathways involved in proliferation, invasion and apoptosis and may serve as prognostic and predictive markers. In this study we aimed to evaluate the role of miRNA-148a and miRNA-625-3p in metastatic colorectal cancer. METHODS: Fifty-four patients with a first-time diagnosed CRC receiving FOLFOX ± Bevacizumab were involved in the study. Tumor samples underwent routine pathology examination including evaluation for tumor budding and KRAS. MiRNA-148a and miRNA-625-3p expression analysis was done by RT-PCR. Associations between expression of both miRNAs and clinico-pathological factors, treatment outcomes and survival were analyzed. RESULTS: Both miRNA-148a and miRNA-625-3p were down-regulated in the tumors compared to normal colonic mucosa. Significantly lower expression of both miRNAs was noticed in tumors with budding phenomenon compared to tumors without it (median values of miRNA-148a were 0.314 and 0.753 respectively, p = 0.011, and 0.404 and 0.620 respectively for miRNA-625-3p, p = 0.036). Significantly lower expression of miRNA-625-3p was detected in rectal tumors, compared to tumors in the colon (median 0.390 and 0.665 respectively, p = 0.037). Progression free survival was significantly lower in patients with high miRNA-148a expression (6 and 9 months respectively, p = 0.033), but there were no significant differences in PFS for miRNA-625-3p and in overall survival for both miRNAs. CONCLUSIONS: There was a significant relationship between low miRNA-148a and miRNA-625-3p expression and tumor budding, which is thought to represent epithelial-mesenchymal transition. Both studied miRNAs may be associated with a more aggressive phenotype and could be the potential prognostic and predictive biomarkers in CRC. Further investigation is needed to confirm miRNAs involvement in EMT, and their prognostic and predictive value. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3575-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-55804372017-09-07 Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding Baltruskeviciene, Edita Schveigert, Diana Stankevicius, Vaidotas Mickys, Ugnius Zvirblis, Tadas Bublevic, Jaroslav Suziedelis, Kestutis Aleknavicius, Eduardas BMC Cancer Research Article BACKGROUND: MiRNAs are often deregulated in colorectal cancer and might function as tumor suppressors or as oncogenes. They participate in controlling key signaling pathways involved in proliferation, invasion and apoptosis and may serve as prognostic and predictive markers. In this study we aimed to evaluate the role of miRNA-148a and miRNA-625-3p in metastatic colorectal cancer. METHODS: Fifty-four patients with a first-time diagnosed CRC receiving FOLFOX ± Bevacizumab were involved in the study. Tumor samples underwent routine pathology examination including evaluation for tumor budding and KRAS. MiRNA-148a and miRNA-625-3p expression analysis was done by RT-PCR. Associations between expression of both miRNAs and clinico-pathological factors, treatment outcomes and survival were analyzed. RESULTS: Both miRNA-148a and miRNA-625-3p were down-regulated in the tumors compared to normal colonic mucosa. Significantly lower expression of both miRNAs was noticed in tumors with budding phenomenon compared to tumors without it (median values of miRNA-148a were 0.314 and 0.753 respectively, p = 0.011, and 0.404 and 0.620 respectively for miRNA-625-3p, p = 0.036). Significantly lower expression of miRNA-625-3p was detected in rectal tumors, compared to tumors in the colon (median 0.390 and 0.665 respectively, p = 0.037). Progression free survival was significantly lower in patients with high miRNA-148a expression (6 and 9 months respectively, p = 0.033), but there were no significant differences in PFS for miRNA-625-3p and in overall survival for both miRNAs. CONCLUSIONS: There was a significant relationship between low miRNA-148a and miRNA-625-3p expression and tumor budding, which is thought to represent epithelial-mesenchymal transition. Both studied miRNAs may be associated with a more aggressive phenotype and could be the potential prognostic and predictive biomarkers in CRC. Further investigation is needed to confirm miRNAs involvement in EMT, and their prognostic and predictive value. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3575-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-09-01 /pmc/articles/PMC5580437/ /pubmed/28863773 http://dx.doi.org/10.1186/s12885-017-3575-z 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
Baltruskeviciene, Edita
Schveigert, Diana
Stankevicius, Vaidotas
Mickys, Ugnius
Zvirblis, Tadas
Bublevic, Jaroslav
Suziedelis, Kestutis
Aleknavicius, Eduardas
Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding
title Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding
title_full Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding
title_fullStr Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding
title_full_unstemmed Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding
title_short Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding
title_sort down-regulation of mirna-148a and mirna-625-3p in colorectal cancer is associated with tumor budding
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580437/
https://www.ncbi.nlm.nih.gov/pubmed/28863773
http://dx.doi.org/10.1186/s12885-017-3575-z
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