Down-regulated SOX4 Expression Suppresses Cell Proliferation, Metastasis and Induces Apoptosis inXuanwei Female Lung Cancer Patients
Down-regulated SOX4 Expression Suppresses Cell Proliferation, Metastasis and Induces Apoptosis inXuanwei Female Lung Cancer Patients
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宣威女性肺癌患者SOX4表达下调抑制细胞增殖、转移并诱导细胞凋亡
DOI：
10.1002/jcb.25055
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发表时间：
2015
影响因子：
4
通讯作者：
Guangjian Li
中科院分区：
文献类型：
--
作者：
Yongchun Zhou;Xicai Wang;Yunchao Huang;Yan Chen;Guangqiang Zhao;Qian Yao;Congguo Jin;Youguang Huang;Xin Liu;Guangjian Li
转录因子SOX 4在胎儿肺成熟和许多癌症的肿瘤发生中具有重要的功能。然而，其在肺肿瘤发生发展中的生物学功能仍不清楚。在本研究中，我们发现SOX 4 mRNA和蛋白在宣威女性肺癌组织中的表达水平显著高于肺良性病变。SOX 4蛋白高表达组的病理分级、淋巴结转移、肿瘤分化程度和预后均高于低表达组。SOX 4基因在宣威女性肺癌细胞系XWLC-05中的敲低导致凋亡形态学改变，细胞增殖、侵袭和迁移降低。此外，敲低SOX 4基因导致明显的亚G1峰，并通过上调caspase-3表达诱导细胞凋亡，而在用caspase-3抑制剂处理的细胞中，通过沉默SOX 4表达诱导的细胞凋亡被抑制。裸鼠体内分析进一步证实，敲低SOX 4抑制肿瘤生长。结论：SOX 4基因可能是宣威女性肺癌细胞增殖、凋亡和转移的重要抑癌基因，有望成为肺癌有效治疗的靶点。J.细胞。116：1007-1018，2015.© 2015威利期刊公司.
The transcription factor SOX4 has functional importance in foetal lung maturation and tumorigenesis in a number of cancers. However, its biological functions in the progression of lung tumorigenesis remain unclear. In this study, we found that the expression levels of SOX4 mRNA and protein were significantly higher in Xuanwei female lung cancer tissues than in benign lung lesions. The patients with high expression of the SOX4 protein had a higher pathological grade, lymph node (LN) metastasis, poor tumor differentiation and worse prognosis than those patients with low expression of SOX4. Knockdown of the SOX4 gene in the Xuanwei female lung cancer cell line XWLC‐05 resulted in apoptotic morphological changes, decreased cell proliferation, invasion and migration. Furthermore, knockdown of the SOX4 gene resulted in obvious sub‐G1 peaks and induction of apoptosis through upregulation of caspase‐3 expression, while in cells treated with a caspase‐3 inhibitor, apoptosis induced by silencing SOX4 expression was inhibited. In vivo analysis in nude mice further confirmed that knockdown of SOX4 suppressed tumor growth. In conclusion, SOX4 appears to be an important tumor suppressor gene in the regulation of Xuanwei female lung cancer cell proliferation, apoptosis and metastases, and it may be a potential target for effective lung cancer therapy. J. Cell. Biochem. 116: 1007–1018, 2015. © 2015 Wiley Periodicals, Inc.