Functional Analysis and Clinical Significance of Glutaredoxin 2 in Colon Cancer.

Abstract

Glutaredoxin 2 (Grx2) is a member of the glutaredoxin family of proteins, which maintain cellular thiol homeostasis. Grxs is reported to be involved in tumor progression in various cancers. However, the expression and role of Grx2 in colon cancer remain unexplored. This study aimed to clarify the relationship between Grx2 expression and tumor progression in colon cancer. Grx2-knockdown experiments were performed using two human colon cancer cell lines, and the effects on cell proliferation, cell cycle, cell migration, and cell survival were examined. Furthermore, to assess changes in gene profile, mRNA microarray analysis was performed. Samples from 141 patients with colon cancer were subjected to immunohistochemistry for Grx2, and the Grx2 expression prognostic value was analyzed. Grx2 knockdown significantly suppressed cell proliferation with G₀/G₁ arrest, induced apoptosis, and cell migration inhibition in two cell lines. Analysis of the mRNA microarray showed that Grx2 gene expression was densely related to the signaling pathway of G₁/S cell cycle checkpoint regulation, including the Cdk2, Cdk6, and E2F7 genes. Survival analysis showed that high Grx2 expression was significantly associated with poor prognosis, and multivariate analysis identified high Grx2 expression as an independent prognostic factor for patients with colon cancer. Grx2 plays an oncogenic role in colon cancer cells and also affects the relapse-free survival of patients with colon cancer. Grx2 may be a novel prognostic biomarker and therapeutic target for colon cancer.