Classic SRY-box protein SOX7 functions as a tumor suppressor regulating WNT signaling and is methylated in renal cell carcinoma

SOX7 (SRY-related high mobility group box 7), a high mobility group protein, is reported to be down-regulated in several cancer types, which indicates an important role in tumorigenesis; however, its biologic role in renal cell carcinoma (RCC) pathogenesis remains unknown. We studied the alterations and functions of SOX7 in RCC. We detected its broad expression in multiple human normal tissues, including kidney, but frequent down-regulation in RCC cell lines and primary tumors. Promoter CpG methylation seems to directly mediate SOX7 silencing in RCC cells, which could be reversed by demethylation treatment. SOX7 methylation was detected in primary RCC tumors, but rarely in normal kidney tissues. Restoration of SOX7 in silenced 786-O and A498 RCC cell lines inhibited their cell growth by inducing G(0)/G(1) arrest, whereas SOX7 knockdown promoted RCC cell proliferation. We also found that SOX7 silencing resulted in the activation of WNT signaling and the induction of epithelial to mesenchymal transition. In conclusion, the current study demonstrates that SOX7 is frequently inactivated by promoter CpG methylation in RCC and functions as a tumor suppressor by regulating WNT signaling.Wang, L., Fan, Y., Zhang, L., Li, L., Kuang, G., Luo, C., Li, C., Xiang, T., Tao, Q., Zhang, Q., Ying, J. Classic SRY-box protein SOX7 functions as a tumor suppressor regulating WNT signaling and is methylated in renal cell carcinoma.