Silencing GPX3 Expression Promotes Tumor Metastasis in Human Thyroid Cancer

The incidence of thyroid cancer has been increased in the past few decades. GPX3 gene is located in 5q23, which is frequently deleted in prostate cancer. Methylation of GPX3 was found frequently in prostate, esophagus, gastric and breast cancers. To detect the expression and analyze the mechanism of GPX3 in human thyroid cancer, 94 cases of primary papillary thyroid cancer (PTC) which coupled with adjacent tissue samples, as well as 15 cases of normal thyroid epithelial tissue samples were collected. Methylation specific PCR (MSP), immunohistochemistry staining, transwell assay and siRNA knockdown technique were employed. GPX3 was methylated in 46.8% (44 of 94) of PTC and methylation of GPX3 was associated with tumor size (P<0.05) and regional lymph node metastasis (P<0.01) significantly. Consistent expression of GPX3 was observed in the adjacent tissue samples and absent/reduced expression of GPX3 was found frequently in primary PTC samples. In 44 cases of methylated cancer samples, loss of/ reduced expression was found in 36 cases and expression of GPX3 was found in 8 cases. In 50 cases of unmethylated PTC samples, loss of/ reduced expression was found in 31 cases and expression of GPX3 was found in 19 cases. Lost/ reduced expression of GPX3 is associated with promoter region hypermethylation (P<0.05). Wnt signaling was inhibited by GPX3 in TPC-1 and FTC133 cells. In conclusion, GPX3 is frequently methylated in human papillary thyroid cancer and the expression of GPX3 was regulated by promoter region methylation. Methylation of GPX3 is related to tumor size and lymph node metastasis. Metastasis of thyroid cancer was suppressed by GPX3 through inhibition Wnt/β-catenin signaling. Keywords: DNA methylation, glutathione peroxidase 3, metastasis, thyroid cancer, Wnt/β-catenin signaling.