miR-146a polymorphism (rs2910164) predicts colorectal cancer patients' susceptibility to liver metastasis

Tomohiro Iguchi, Sho Nambara, Takaaki Masuda, Hisateru Komatsu, Masami Ueda, Shinya Kidogami, Yushi Ogawa, Qingjiang Hu, Kuniaki Sato, Tomoko Saito, Hidenari Hirata, Shotaro Sakimura, Ryutaro Uchi, Naoki Hayashi, Shuhei Ito, Hidetoshi Eguchi, Keishi Sugimachi, Yoshihiko Maehara, Koshi Mimori

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23 Citations (Scopus)


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.

Original languageEnglish
Article numbere0165912
JournalPloS one
Issue number11
Publication statusPublished - Nov 2016

All Science Journal Classification (ASJC) codes

  • General


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