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SOX12 promotes the growth of multiple myeloma cells by enhancing Wnt/β-catenin signaling.
Experimental Cell Research ( IF 3.3 ) Pub Date : 2020-01-02 , DOI: 10.1016/j.yexcr.2020.111814 Ying Gao 1 , Lan Li 1 , Limin Hou 1 , Ben Niu 1 , Xingli Ru 1 , Ding Zhang 1
Experimental Cell Research ( IF 3.3 ) Pub Date : 2020-01-02 , DOI: 10.1016/j.yexcr.2020.111814 Ying Gao 1 , Lan Li 1 , Limin Hou 1 , Ben Niu 1 , Xingli Ru 1 , Ding Zhang 1
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SRY-related high-mobility-group box 12 (SOX12) has currently emerged as a key cancer-related protein in multiple human cancer types. However, little is known about the relevance of SOX12 in multiple myeloma (MM). The current study aimed to investigate the potential role of SOX12 in MM. Our results demonstrated that SOX12 expression was markedly elevated in MM cell lines. A series of cellular assays demonstrated that SOX12 knockdown significantly reduced the proliferation and colony formation, and upregulated cell apoptosis of MM cells. By contrast, SOX12 overexpression promoted the proliferation, colony formation and decreased the apoptosis of MM cells, results that reveal its oncogenic effects. SOX12 regulated β-catenin expression and TCF/LEF transcriptional activity. Moreover, the SOX12-knockdown-mediated antitumor effect in MM cells was significantly reversed by transfecting a β-catenin expression vector. Notably, SOX12 inhibition retarded tumor growth in vivo of a MM-derived mouse xenograft model. In conclusion, our results suggest a potential oncogenic function for SOX12 in MM. Our findings reveal that SOX12 knockdown inhibits the growth of MM cells by downregulating the Wnt/β-catenin signaling pathway, results that imply SOX12 may represent a novel therapeutic target for MM treatment.
中文翻译：
SOX12通过增强Wnt /β-catenin信号传导来促进多发性骨髓瘤细胞的生长。
SRY相关的高迁移率族盒12（SOX12）目前已成为多种人类癌症类型中与癌症相关的关键蛋白。但是，关于多发性骨髓瘤（MM）中SOX12的相关性知之甚少。当前的研究旨在调查SOX12在MM中的潜在作用。我们的结果表明，MM细胞系中SOX12的表达明显升高。一系列细胞测定表明，SOX12敲低显着降低了MM细胞的增殖和集落形成，并上调了细胞凋亡。相比之下，SOX12的过表达促进了MM细胞的增殖，集落形成并降低了其凋亡，这表明了它的致癌作用。SOX12调节β-catenin表达和TCF / LEF转录活性。而且，通过转染β-catenin表达载体，可显着逆转MMX细胞中SOX12敲低介导的抗肿瘤作用。值得注意的是，SOX12抑制作用可延缓MM衍生的小鼠异种移植模型的体内肿瘤生长。总之，我们的结果表明，MM中SOX12具有潜在的致癌作用。我们的发现表明，SOX12敲低可以通过下调Wnt /β-catenin信号传导途径来抑制MM细胞的生长，结果表明SOX12可能代表了MM治疗的新型治疗靶点。
更新日期：2020-01-02
中文翻译：
SOX12通过增强Wnt /β-catenin信号传导来促进多发性骨髓瘤细胞的生长。
SRY相关的高迁移率族盒12（SOX12）目前已成为多种人类癌症类型中与癌症相关的关键蛋白。但是，关于多发性骨髓瘤（MM）中SOX12的相关性知之甚少。当前的研究旨在调查SOX12在MM中的潜在作用。我们的结果表明，MM细胞系中SOX12的表达明显升高。一系列细胞测定表明，SOX12敲低显着降低了MM细胞的增殖和集落形成，并上调了细胞凋亡。相比之下，SOX12的过表达促进了MM细胞的增殖，集落形成并降低了其凋亡，这表明了它的致癌作用。SOX12调节β-catenin表达和TCF / LEF转录活性。而且，通过转染β-catenin表达载体，可显着逆转MMX细胞中SOX12敲低介导的抗肿瘤作用。值得注意的是，SOX12抑制作用可延缓MM衍生的小鼠异种移植模型的体内肿瘤生长。总之，我们的结果表明，MM中SOX12具有潜在的致癌作用。我们的发现表明，SOX12敲低可以通过下调Wnt /β-catenin信号传导途径来抑制MM细胞的生长，结果表明SOX12可能代表了MM治疗的新型治疗靶点。
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