Zhou Yongchun, Wang Xicai, Huang Yunchao, Chen Yan, Zhao Guangqiang, Yao Qian, Jin Congguo, Huang Youguang, Liu Xin, Li Guangjian
Key Laboratory of Lung Cancer Research of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, PR China.
J Cell Biochem. 2015 Jun;116(6):1007-18. doi: 10.1002/jcb.25055.
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.
转录因子SOX4在胎儿肺成熟以及多种癌症的肿瘤发生过程中具有重要功能。然而，其在肺癌发生发展过程中的生物学功能仍不清楚。在本研究中，我们发现SOX4 mRNA和蛋白的表达水平在宣威女性肺癌组织中显著高于良性肺病变组织。SOX4蛋白高表达的患者比SOX4低表达的患者具有更高的病理分级、淋巴结转移、肿瘤分化差及更差的预后。在宣威女性肺癌细胞系XWLC-05中敲低SOX4基因导致凋亡形态学改变、细胞增殖、侵袭和迁移能力下降。此外，敲低SOX4基因导致明显的亚G1峰，并通过上调caspase-3表达诱导凋亡，而在用caspase-3抑制剂处理的细胞中，沉默SOX4表达诱导的凋亡受到抑制。裸鼠体内分析进一步证实敲低SOX4可抑制肿瘤生长。总之，SOX4似乎是调控宣威女性肺癌细胞增殖、凋亡和转移的重要肿瘤抑制基因，并且它可能是有效的肺癌治疗的潜在靶点。
