A Functional Variant of IC53 Correlates with the Late Onset of Colorectal Cancer

Jingzhou Chen,Xiaojian Wang,Jiafu Ji,Rutai Hui,Yi Shi,Yisong Zhen,Hui Yu,Yinhui Zhang,Ziyu Li,Kejia Lou,Guiguo Zhang,Yan Song,Kai Sun,Yu Han,Ying Hu,Tao Yang

doi:10.2119/molmed.2010.00192

Abstract

The IC53 gene was reported to be upregulated in the colon adenocarcinoma cell line SW480. Here, we show that the expression level of IC53 is positively correlated with the grade and depth of invasion in adenocarcinoma of the colon. Injection of IC53 stably transfected HCT-116 cells into athymic nude mice promoted tumor growth. Furthermore, overexpression of IC53 increased cell invasive growth, which could be dramatically prevented by knocking down IC53 with siRNA. The effects of IC53 on cell-invasive growth were mediated by upregulation of integrins, activation of phosphatidylinositol 3-kinase and phosphorylation of Akt. A single-nucleotide polymorphism rs2737 in the IC53 gene created a potential microRNA379 target site, and microRNA379 expression inhibited IC53 translation. Among 222 patients with colorectal cancer, the C/C rs2737 genotype was associated with late onset of colorectal cancer (median age 63.0 versus 55.3 years, P = 0.003). The frequency of the C/C rs2737 genotype was much lower in patients who developed colorectal cancer below the age of 45 years than in individuals over age 45 years (10.8% versus 26.6%, P = 0.039). These data indicated that IC53 is a positive mediator for colon cancer progression, and IC53-rs2737 may serve as protection from the onset of colorectal cancer.

Highlights

Colorectal cancer (CRC) is one of the most common cancers in industrialized countries
To confirm whether IC53 is expressed in normal colon epithelial, we performed immunohistochemistry, showing that IC53 was low or weak when expressed in the normal colon epithelial (Supplementary Figure S2)
We found a strong correlation between the IC53 expression level and the grade of adenocarcinoma of the colon, a weak association between the IC53 expression level and the degree of invasion and no association between the IC53 expression level and the grade or the degree of mucinous carcinoma of the colon (P = 0.13 and P = 0.27, see Table 1)

Summary

Introduction

Colorectal cancer (CRC) is one of the most common cancers in industrialized countries. Because IC53 is upregulated in colon cancer and promotes colon cancer cell proliferation, migration and adhesion, we investigated the target genes that are important in the mediation of IC53-regulated cell invasive growth.

Results

Conclusion