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 Y. K. 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.
FASEB J. 2019 Jan;33(1):254-263. doi: 10.1096/fj.201701453RR. Epub 2018 Jun 29.
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/G 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.
SOX7（SRY 相关高迁移率族盒 7）是一种高迁移率族蛋白，据报道在几种癌症类型中下调，这表明其在肿瘤发生中具有重要作用；然而，其在肾细胞癌（RCC）发病机制中的生物学作用尚不清楚。我们研究了 SOX7 在 RCC 中的改变和功能。我们检测到其在多种人类正常组织中广泛表达，包括肾脏，但在 RCC 细胞系和原发性肿瘤中频繁下调。启动子 CpG 甲基化似乎直接介导 RCC 细胞中 SOX7 的沉默，这种沉默可以通过去甲基化处理逆转。SOX7 甲基化在原发性 RCC 肿瘤中检测到，但在正常肾脏组织中很少检测到。沉默的 786-O 和 A498 RCC 细胞系中 SOX7 的恢复通过诱导 G1/G0 期阻滞抑制其细胞生长，而 SOX7 的敲低促进了 RCC 细胞的增殖。我们还发现 SOX7 沉默导致 WNT 信号的激活和上皮间质转化的诱导。总之，本研究表明，SOX7 在 RCC 中经常因启动子 CpG 甲基化而失活，并通过调节 WNT 信号发挥肿瘤抑制作用。
