Sun Chuntao, Ban Yunqing, Wang Kai, Sun Yanming, Zhao Zhihua
Department of Interventional Radiology, Weifang City People's Hospital, Weifang, Shandong 261041, P.R. China.
Imaging Center, The 5th Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
Oncol Lett. 2019 Mar;17(3):2754-2762. doi: 10.3892/ol.2019.9914. Epub 2019 Jan 9.
Sex determining region Y-box protein 5 (SOX5) is a transcriptional factor and serves important roles in various cancer types; however, the pathological role of SOX5 in patients with breast cancer remains unclear. In the present study, the expression and potential role of SOX5 in patients with breast cancer and in breast cancer cells was investigated. The data indicated that SOX5 was highly expressed in breast cancer tissues compared with adjacent healthy tissues, and overexpression of SOX5 was associated with a reduced overall survival rate in patients with breast cancer. Gain and loss of function studies with MTT, colony formation, wound healing and Matrigel invasion assays demonstrated that SOX5 significantly promoted breast cancer cell proliferation and invasion. The chromatin immunoprecipitation (ChIP) assay sequence, quantitative ChIP and luciferase reporter assays were used to identify enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) as a downstream target gene of SOX5. Furthermore, it was determined that ectopic expression of SOX5 increased EZH2 expression at the mRNA and protein level, while the knockdown of SOX5 decreased EZH2 expression. Additionally, the biological effect of SOX5 was investigated, and it was determined to be dependent on the regulation of EZH2 expression. The present results may provide important insights into the biological significance of SOX5 serving as a candidate therapeutic target in breast cancer progression.
Y染色体性别决定区盒蛋白5（SOX5）是一种转录因子，在多种癌症类型中发挥重要作用；然而，SOX5在乳腺癌患者中的病理作用仍不清楚。在本研究中，对SOX5在乳腺癌患者及乳腺癌细胞中的表达及潜在作用进行了研究。数据表明，与相邻健康组织相比，SOX5在乳腺癌组织中高表达，且SOX5的过表达与乳腺癌患者总生存率降低相关。通过MTT、集落形成、伤口愈合和基质胶侵袭实验进行的功能获得和缺失研究表明，SOX5显著促进乳腺癌细胞增殖和侵袭。采用染色质免疫沉淀（ChIP）分析序列、定量ChIP和荧光素酶报告基因实验，以鉴定zeste增强子2多梳抑制复合物2亚基（EZH2）为SOX5的下游靶基因。此外，还确定SOX5的异位表达在mRNA和蛋白质水平上增加了EZH2的表达，而敲低SOX5则降低了EZH2的表达。另外，对SOX5的生物学效应进行了研究，确定其依赖于对EZH2表达的调控。本研究结果可能为SOX5作为乳腺癌进展中候选治疗靶点的生物学意义提供重要见解。
