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 G0/G1 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.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2018 Jun 29 [Epub ahead of print]

Lu Wang, Yu Fan, Lian Zhang, Lili Li, Guanyu Kuang, Cheng Luo, Chen Li, Tingxiu Xiang, Qian Tao, Qian Zhang, Jianming Ying

Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China., Cancer Epigenetics Laboratory, State Key Laboratory of Oncology in South China, Department of Clinical Oncology, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong and Chinese University of Hong Kong Shenzhen Research Institute, Hong Kong, China., Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.