miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients' Susceptibility to Liver Metastasis.
miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients' Susceptibility to Liver Metastasis.
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DOI：
10.1371/journal.pone.0165912
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Mimori K
中科院分区：
文献类型：
--
作者：
Iguchi T;Nambara S;Masuda T;Komatsu H;Ueda M;Kidogami S;Ogawa Y;Hu Q;Sato K;Saito T;Hirata H;Sakimura S;Uchi R;Hayashi N;Ito S;Eguchi H;Sugimachi K;Maehara Y;Mimori K
miR-146 a在癌症中起着重要作用，因为它直接靶向NUMB，NUMB是Notch信号传导的抑制剂。据报道，miR-146 a受G>C多态性（SNP; rs 2910164）调控。这种多态性影响各种癌症，包括结直肠癌（CRC）。然而，miR-146 a多态性在结直肠癌中的临床意义尚不清楚。根据miR-146 a多态性，将59例CRC患者分为2组：CC/CG基因型（n = 32）和GG基因型（n = 27）。使用59个临床样本进行cDNA微阵列分析。使用GSEA提取每个基因型中显著富集的基因集。我们还研究了miR-146 a多态性与CRC细胞系中miR-146 a、NUMB表达或迁移反应之间的关联。CC/CG基因型与显著更多的同步肝转移相关（p = 0.007）。两种基因型的热图显示表达谱明显分层。GSEA表明Notch信号传导和JAK/STAT 3信号传导与CC/CG基因型显著相关（分别为p = 0.004和p = 0.023）。具有pre-miR-146 a/C的CRC细胞系显示出显著更高的miR-146 a表达（p = 0.034）和更高的NUMB表达和趋化活性。在CRC中，miR-146 a多态性参与肝转移。这种多态性的鉴定可能有助于确定CRC肝转移高风险患者。
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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DOI：
10.1016/j.bbrc.2008.11.041
发表时间：
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