Abstract
BackgroundAlthough Argonaute proteins are considered to play important roles in stem cell self-renewal, RNA interference (RNAi) and translational regulation, relatively little is known about their functions in human disease. In this study, we investigated the expression of eight members of human Argonaute family in colon cancer and identified their potential roles in tumor development and progression.MethodsAntibodies against human Argonaute proteins were prepared by immunizing rabbits with synthetic peptides derived from the sequences of Argonaute members. Then we constructed a tissue microarray containing 75 specimens from colon cancer and 75 specimens from adjacent non-cancer tissue, and assayed eight different proteins (EIF2C1, EIF2C2, EIF2C3, EIF2C4, PIWIL1, PIWIL2, PIWIL3 and PIWIL4) by immunohistochemistry on consecutive formalin-fixed tissue microarray sections.ResultsThe expression of EIF2C1-4 and PIWIL1-4 was significantly higher in tumorous tissue than in adjacent tissue. Notably, a significant correlation was observed between the positive expression of EIF2C2, EIF2C3, EIF2C4, PIWIL4 and the presence of distant metastasis. Logistic regression analysis revealed that an increased expression of EIF2C1 and PIWIL2 was significantly associated with occurrence of colon cancer tissue compared with non-cancer tissue.ConclusionsArgonaute proteins are overexpressed in colon cancer relative to adjacent non-cancer tissue. The expression of EIF2C2-4 and PIWIL4 appears increased in advanced tumors with distant metastasis, suggesting it may promote tumor invasion. Furthermore, EIF2C1 and PIWIL2 might represent novel colon cancer markers with early diagnostic significance.
Highlights
Argonaute proteins are considered to play important roles in RNA interference, stem cell selfrenewal and translational regulation, relatively little is known about their functions in human disease
We found the positive correlation of EIF2C2, EIF2C3, EIF2C4 and PIWIL4 with tumor distant metastasis
Of the EIF2C1-4 and PIWIL1-4 analyzed by logistic regression, we observed that an increased expression of EIF2C1 and PIWIL2 was significantly associated with occurrence of colon cancer tissue compared with non-cancer tissue
Summary
Argonaute proteins are considered to play important roles in stem cell self-renewal, RNA interference (RNAi) and translational regulation, relatively little is known about their functions in human disease. We investigated the expression of eight members of human Argonaute family in colon cancer and identified their potential roles in tumor development and progression. Colon cancer may be considered the final step of a progressive imbalance between mucosal cell proliferation and apoptosis due to the activation of oncogenes and the inactivation of tumor suppressor genes [3,4,5]. The evaluation of the clinical utility of each of these genes would require multiple consecutive experiments with hundreds of tumor specimens. This would be both time-consuming as well as impractical for more than a handful of genes. Microarray technology provides a new and promising tool that allows the detection of a large variety of parameters simultaneously, and will be of importance in the fight against colon cancer
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