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miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis
miR-146a plays important roles in cancer as it directly targets NUMB, an inhibitor of Notch signaling. miR-146a is reportedly regulated by a G>C polymorphism (SNP; rs2910164). This polymorphism affects various cancers, including colorectal cancer (CRC). However, the clinical significance of miR-1...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100922/ https://www.ncbi.nlm.nih.gov/pubmed/27824903 http://dx.doi.org/10.1371/journal.pone.0165912 |
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author | Iguchi, Tomohiro Nambara, Sho Masuda, Takaaki Komatsu, Hisateru Ueda, Masami Kidogami, Shinya Ogawa, Yushi Hu, Qingjiang Sato, Kuniaki Saito, Tomoko Hirata, Hidenari Sakimura, Shotaro Uchi, Ryutaro Hayashi, Naoki Ito, Shuhei Eguchi, Hidetoshi Sugimachi, Keishi Maehara, Yoshihiko Mimori, Koshi |
author_facet | Iguchi, Tomohiro Nambara, Sho Masuda, Takaaki Komatsu, Hisateru Ueda, Masami Kidogami, Shinya Ogawa, Yushi Hu, Qingjiang Sato, Kuniaki Saito, Tomoko Hirata, Hidenari Sakimura, Shotaro Uchi, Ryutaro Hayashi, Naoki Ito, Shuhei Eguchi, Hidetoshi Sugimachi, Keishi Maehara, Yoshihiko Mimori, Koshi |
author_sort | Iguchi, Tomohiro |
collection | PubMed |
description | miR-146a plays important roles in cancer as it directly targets NUMB, an inhibitor of Notch signaling. miR-146a is reportedly regulated by a G>C polymorphism (SNP; rs2910164). This polymorphism affects various cancers, including colorectal cancer (CRC). However, the clinical significance of miR-146a polymorphism in CRC remains unclear. A total of 59 patients with CRC were divided into 2 groups: a CC/CG genotype (n = 32) and a GG genotype (n = 27), based on the miR-146a polymorphism. cDNA microarray analysis was performed using 59 clinical samples. Significantly enriched gene sets in each genotype were extracted using GSEA. We also investigated the association between miR-146a polymorphism and miR-146a, NUMB expression or migratory response in CRC cell lines. The CC/CG genotype was associated with significantly more synchronous liver metastasis (p = 0.007). A heat map of the two genotypes showed that the expression profiles were clearly stratified. GSEA indicated that Notch signaling and JAK/STAT3 signaling were significantly associated with the CC/CG genotype (p = 0.004 and p = 0.023, respectively). CRC cell lines with the pre-miR-146a/C revealed significantly higher miR-146a expression (p = 0.034) and higher NUMB expression and chemotactic activity. In CRC, miR-146a polymorphism is involved in liver metastasis. Identification of this polymorphism could be useful to identify patients with a high risk of liver metastasis in CRC. |
format | Online Article Text |
id | pubmed-5100922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-51009222016-11-18 miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis Iguchi, Tomohiro Nambara, Sho Masuda, Takaaki Komatsu, Hisateru Ueda, Masami Kidogami, Shinya Ogawa, Yushi Hu, Qingjiang Sato, Kuniaki Saito, Tomoko Hirata, Hidenari Sakimura, Shotaro Uchi, Ryutaro Hayashi, Naoki Ito, Shuhei Eguchi, Hidetoshi Sugimachi, Keishi Maehara, Yoshihiko Mimori, Koshi PLoS One Research Article miR-146a plays important roles in cancer as it directly targets NUMB, an inhibitor of Notch signaling. miR-146a is reportedly regulated by a G>C polymorphism (SNP; rs2910164). This polymorphism affects various cancers, including colorectal cancer (CRC). However, the clinical significance of miR-146a polymorphism in CRC remains unclear. A total of 59 patients with CRC were divided into 2 groups: a CC/CG genotype (n = 32) and a GG genotype (n = 27), based on the miR-146a polymorphism. cDNA microarray analysis was performed using 59 clinical samples. Significantly enriched gene sets in each genotype were extracted using GSEA. We also investigated the association between miR-146a polymorphism and miR-146a, NUMB expression or migratory response in CRC cell lines. The CC/CG genotype was associated with significantly more synchronous liver metastasis (p = 0.007). A heat map of the two genotypes showed that the expression profiles were clearly stratified. GSEA indicated that Notch signaling and JAK/STAT3 signaling were significantly associated with the CC/CG genotype (p = 0.004 and p = 0.023, respectively). CRC cell lines with the pre-miR-146a/C revealed significantly higher miR-146a expression (p = 0.034) and higher NUMB expression and chemotactic activity. In CRC, miR-146a polymorphism is involved in liver metastasis. Identification of this polymorphism could be useful to identify patients with a high risk of liver metastasis in CRC. Public Library of Science 2016-11-08 /pmc/articles/PMC5100922/ /pubmed/27824903 http://dx.doi.org/10.1371/journal.pone.0165912 Text en © 2016 Iguchi 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Iguchi, Tomohiro Nambara, Sho Masuda, Takaaki Komatsu, Hisateru Ueda, Masami Kidogami, Shinya Ogawa, Yushi Hu, Qingjiang Sato, Kuniaki Saito, Tomoko Hirata, Hidenari Sakimura, Shotaro Uchi, Ryutaro Hayashi, Naoki Ito, Shuhei Eguchi, Hidetoshi Sugimachi, Keishi Maehara, Yoshihiko Mimori, Koshi miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis |
title | miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis |
title_full | miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis |
title_fullStr | miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis |
title_full_unstemmed | miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis |
title_short | miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis |
title_sort | mir-146a polymorphism (rs2910164) predicts colorectal cancer patients’ susceptibility to liver metastasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100922/ https://www.ncbi.nlm.nih.gov/pubmed/27824903 http://dx.doi.org/10.1371/journal.pone.0165912 |
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