miR-146a Polymorphism (rs2910164) Predicts Colorectal Cancer Patients’ Susceptibility to Liver Metastasis

Abstract

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.

Restoration of miR-193a-5p and miR-146 a-5p Expression Induces G1 Arrest in Colorectal Cancer through Targeting of MDM2/p53

“…17,18 Recently, abnormal miRNA expression profiles in multiple cancers including CRC have been reported by numerous studies. 19 According to several studies, the expression levels of miR-193a-5p and miR-146a-5p are substantially reduced in CRC 8,20 ; these findings were confirmed by the results of our study. In the present study, we observed that replacement of miR-193a-5p and miR-146a-5p individually and simultaneously in HT-29 CRC cell line reduced the ratio of MDM2 protein.…”

Association between miRNA polymorphisms and susceptibility to brain tumors

“…For example, Iguchi et al observed colorectal cancer cell lines with the pre-miR-146a GG genotype exhibited significantly lower expression of miR-146a compared with those with the GC/CC genotype. [20] Yamashita et al proved proliferation, migration, and invasion abilities were significantly higher in human melanoma cell lines with the G allele than those with the C allele. [21] The study of Wang et al showed that individuals carrying the C allele had increased expression levels of miR-146a compared with those carrying the G allele.…”

miR-146a promotes growth of osteosarcoma cells by targeting ZNRF3/GSK-3β/β-catenin signaling pathway

“…Accumulating evidence shows that miR-146a is implicated in cell growth and metastasis in various cancers, of which the dysregulation of miR-146a is associated with pathological staging, poor differentiation and distant metastasis, acting as an independent prognostic element for overall survival in gastric cancer [ 25 , 26 ] and lung cancer [ 27 ]. In addition, miR-146a polymorphism rs2910164 is linked to the risk of esophageal cancer and colorectal cancers [ 28 , 29 ]. In this study, we analyzed the correlation of miR-146a with clinicopathologic characteristics and prognosis of OS patients, which indicated that increased expression of miR-146a was positively linked to tumor size and OS recurrence, but Kaplan-Meier analysis indicated that miR-146a was not an independent prognostic factor for overall survival and recurrence for OS patients, unveiling that miR-146a might be a potential biomarker for OS patients.…”