Classic SRY-box protein SOX7 functions as a tumor suppressor regulating WNT signaling and is methylated in renal cell carcinoma
Classic SRY-box protein SOX7 functions as a tumor suppressor regulating WNT signaling and is methylated in renal cell carcinoma
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经典的 SRY-box 蛋白 SOX7 作为肿瘤抑制因子调节 WNT 信号传导，并在肾细胞癌中被甲基化
DOI：
10.1096/fj.201701453rr
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发表时间：
2019-01-01
期刊：
影响因子：
4.8
通讯作者：
Ying, Jianming
中科院分区：
文献类型：
--
作者：
Wang, Lu;Fan, Yu;Ying, Jianming
SOX 7（SRY相关高迁移率族蛋白7）是一种高迁移率族蛋白，在多种肿瘤中表达下调，在肿瘤发生中起重要作用，但其在肾细胞癌（RCC）发病机制中的生物学作用尚不清楚。我们研究了SOX 7在肾细胞癌中的变化及其功能。我们检测到它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细胞中的SOX 7沉默，这可以通过去甲基化处理来逆转。SOX 7甲基化在原发性RCC肿瘤中检测到，但在正常肾组织中很少。在沉默的786-O和A498 RCC细胞系中，SOX 7的恢复通过诱导G（0）/G（1）停滞来抑制其细胞生长，而SOX 7的敲低促进RCC细胞增殖。我们还发现，SOX 7沉默导致WNT信号的激活和上皮细胞向间充质细胞转化的诱导。总之，目前的研究表明，SOX 7在RCC中经常被启动子CpG甲基化失活，并通过调节WNT信号传导作为肿瘤抑制因子发挥作用。范，Y.，张，L.，Li，L.，Kuang，G.，Luo，C.，（1995 - 1996），中国地质大学，Li，C.，Xiang，T.，陶，Q，张，Q，Ying，J.经典SRY-box蛋白SOX 7作为肿瘤抑制因子调节WNT信号传导并在肾细胞癌中甲基化。
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.