TY - JOUR
T1 - miR-146a polymorphism (rs2910164) predicts colorectal cancer patients' susceptibility to liver metastasis
AU - Iguchi, Tomohiro
AU - Nambara, Sho
AU - Masuda, Takaaki
AU - Komatsu, Hisateru
AU - Ueda, Masami
AU - Kidogami, Shinya
AU - Ogawa, Yushi
AU - Hu, Qingjiang
AU - Sato, Kuniaki
AU - Saito, Tomoko
AU - Hirata, Hidenari
AU - Sakimura, Shotaro
AU - Uchi, Ryutaro
AU - Hayashi, Naoki
AU - Ito, Shuhei
AU - Eguchi, Hidetoshi
AU - Sugimachi, Keishi
AU - Maehara, Yoshihiko
AU - Mimori, Koshi
N1 - Funding Information:
This work was supported by the following grants and foundations: Grants-in-Aid for Scientific Research of MEXT (26461980, 15H04921, 15K10168, 15K10170). This research used computational resources of the K computer provided by the RIKEN Advanced Institute for Computational Science through the HPCI System Research project (Project ID: hp140230). Computation time was also provided by the Supercomputer System, Human Genome Center, Institute of Medical Science, University of Tokyo ( http://sc.hgc.jp/shirokane.html ). We appreciate the technical support of Ms. Kazumi Oda, Michiko Kasagi, Sachiko Sakuma, Noriko Mishima and Tomoko Kawano.
Publisher Copyright:
© 2016 Iguchi et al. 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 credited.
PY - 2016/11
Y1 - 2016/11
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0165912
DO - 10.1371/journal.pone.0165912
M3 - Article
C2 - 27824903
AN - SCOPUS:84994644636
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 11
M1 - e0165912
ER -
