Down-regulated SOX4 Expression Suppresses Cell Proliferation, Metastasis and Induces Apoptosis in Xuanwei Female Lung Cancer Patients

• Published in: Journal of cellular biochemistry 2015-06, Vol.116 (6), p.1007-1018
• Main Authors: Zhou, Yongchun, Wang, Xicai, Huang, Yunchao, Chen, Yan, Zhao, Guangqiang, Yao, Qian, Jin, Congguo, Huang, Youguang, Liu, Xin, Li, Guangjian
• Format: Article
• Language: English
• Subjects: Animals; APOPTOSIS; Apoptosis - genetics; Apoptosis - physiology; Blotting, Western; Caspase; CASPASE-3; Cell growth; Cell migration; Cell proliferation; Cell Proliferation - physiology; Female; Gene expression; Humans; Immunohistochemistry; LUNG CANCER; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Lymph nodes; Lymphatic Metastasis - genetics; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Electron, Transmission; Middle Aged; Proteins; Real-Time Polymerase Chain Reaction; SOX4; Sox4 protein; SOXC Transcription Factors - genetics; SOXC Transcription Factors - metabolism; Tumor suppressor genes; Tumorigenesis; Tumors
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.25055

ABSTRACT 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.