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Oncogenic role of SOX9 expression in human malignant glioma

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Abstract

SOX9 belongs to the SOX (Sry-related high-mobility group box) family and acts as a transcription factor that plays a central role in the development and differentiation of multiple cell lineages. Recent studies have demonstrated that SOX9 is required for the carcinogenesis in several cancer types. The aim of this study was to investigate the clinicopathological significance of SOX9 expression in human malignant glioma. SOX9 mRNA expression was detected by real-time quantitative RT-PCR assay in glioma and nonneoplastic brain tissues. Then, the association of SOX9 mRNA expression with clinicopathological factors or prognosis of glioma patients was statistically analyzed. In addition, the small interfering RNA was used to knockdown SOX9 expression in a glioma cell line and to analyze the effects of SOX9 inhibition on cell growth, cell cycle and apoptosis of glioma cell line. The expression level of SOX9 mRNA in glioma tissues was significantly higher than that in corresponding nonneoplastic brain tissues (P < 0.001). In addition, a high level of SOX9 mRNA expression was significantly more common in glioma tissues with advanced WHO grade than those with low grade (P = 0.02). The increased expression of SOX9 mRNA was also significantly correlated with low Karnofsky performance score (P = 0.008). Meanwhile, the disease-free and overall survival rates of patients with high SOX9 mRNA expression were obviously lower than those of patients with low SOX9 mRNA expression (both P = 0.01). Multivariate analysis showed that high SOX9 mRNA expression was an independent prognostic factor for glioma patients (P = 0.02). Moreover, the down-regulation of SOX9 could inhibit the cell growth, induce the cell arrest in G2/M phase of cell cycle and enhance the apoptosis in glioma cells. Our data suggest for the first time that the over-expression of SOX9 mRNA is closely associated with poor clinical outcome of patients with malignant gliomas, and targeting SOX9 may be a novel therapeutic strategy for this tumor.

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Acknowledgments

This work was funded by National Natural Science Foundation of China (NO. 81101736) and Talents Supported Plan Foundation of Tangdu Hospital (2011)

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None.

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Author notes

  1. Liang Wang & Shiming He

    Present address: Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi’an City, 710038, People’s Republic of China

Authors and Affiliations

  1. Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi’an City, 710038, People’s Republic of China

    Jianhai Zong

  2. Administrative Department, Tangdu Hospital, Fourth Military Medical University, Xi’an City, 710038, People’s Republic of China

    Jun Yuan & Yongsheng Zhang

  3. Department of Neurosurgery, 254th Hospital of PLA, Tianjin City, 300142, People’s Republic of China

    Xinggang Mao

  4. Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an City, 710038, People’s Republic of China

    Yizhan Cao & Yanyang Tu

Authors
  1. Liang Wang
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  2. Shiming He
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  3. Jun Yuan
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  4. Xinggang Mao
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  5. Yizhan Cao
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  6. Jianhai Zong
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  7. Yanyang Tu
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  8. Yongsheng Zhang
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Corresponding authors

Correspondence to Yanyang Tu or Yongsheng Zhang.

Additional information

Liang Wang, Shiming He, and Jun Yuan contributed equally.

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Wang, L., He, S., Yuan, J. et al. Oncogenic role of SOX9 expression in human malignant glioma. Med Oncol 29, 3484–3490 (2012). https://doi.org/10.1007/s12032-012-0267-z

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  • DOI: https://doi.org/10.1007/s12032-012-0267-z

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