Relationship between expression of XRCC1 and tumor proliferation, migration, invasion, and angiogenesis in glioma

Recently, XRCC1 polymorphisms were reported to be associated with glioma in Chinese population. However, only a few studies reported on the XRCC1 expression, and cancer progression. In this study, we investigated whether XRCC1 plays a role in glioma pathogenesis. Using the tissue microarray technology, we found that XRCC1 expression is significantly decreased in glioma compared with tumor adjacent normal brain tissue (P < 0.01, χ² test) and reduced XRCC1 staining was associated with WHO stages (P < 0.05, χ² test). The mRNA and protein levels of XRCC1 were significantly downregulated in human primary glioma tissues (P < 0.001, χ² test). We also found that XRCC1 was significantly decreased in glioma cell lines compared to normal human astrocytes (P < 0.01, χ² test). Overexpression of XRCC1 dramatically reduced the proliferation and caused cessation of cell cycle. The reduced cell proliferation is due to G1 phase arrest as cyclin D1 is diminished whereas p16 is upregulated. We further demonstrated that XRCC1 overexpression suppressed the glioma cell migration and invasion abilities by targeting MMP-2. In addition, we also found that overexpression of XRCC1 sharply inhibited angiogenesis, which correlated with down-regulation of VEGF. The data indicate that XRCC1 may be a tumor suppressor involved in the progression of glioma.