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Association of SOX4 regulated by tumor suppressor miR-30a with poor prognosis in low-grade chondrosarcoma

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Tumor Biology

Abstract

The sex-determining region Y-box 4 (SOX4), a transcription factor, is involved in various developmental processes. It has been reported in multiple human cancers. However, the prognostic value and its exact role in chondrosarcoma remain poorly understood. In the current study, SOX4 was overexpressed in 28 of 92 (30.4 %) interpretable chondrosarcoma patients compared with 3 of 43 (6.9 %) interpretable chondroma cases (P = 0.003). Its overexpression in chondrosarcoma was significantly associated with histological grade (P < 0.001) and the presence of tumor recurrence (P = 0.041). In addition, SOX4 overexpression was notably correlated with c-MYC (P = 0.011) and P53 (P = 0.029) expression as well as high Ki67 labeling index (LI) (P < 0.001) in our cohort. More importantly, we found that SOX4 was an unfavorable independent prognostic factor for chondrosarcoma patients with low histological grade. Functionally, SOX4 silencing significantly suppressed the proliferation, migratory, and invasive capacity of SW1353 cells, suggesting an oncogenic role of SOX4 in chondrosarcoma in vitro. In an attempt of characterizing SOX4 overexpression mechanism, we identified miR-30a as a tumor suppressor that directly targets SOX4 in chondrosarcoma cells. Clinically, miR-30a expression was negatively correlated with SOX4 expression in chondrosarcoma cases. In all, we identified that SOX4 was oncogenic in chondrosarcoma and negatively regulated by miR-30a in vitro. Importantly, SOX4 overexpression may serve as a prognostic marker for patients with low-histological-grade chondrosarcoma.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81302239), National Natural Science Foundation of Shandong Province (Grant No. ZR2013HM094), Promotive Research Fund for Excellent Young and Middle-Aged Scientists of Shandong Province (Grant No. BS2012YY020), Science Foundation of Shandong Province China (Grant No. ZR2011HQ040), and Independent Innovation Foundation of Shandong University (Grant No. 2012TS121).

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Authors and Affiliations

  1. Department of Pathology, Shandong University Medical School, #44, Wenhua Xi Rd, Jinan, 250012, China

    Ning Lu, Lin Wang, Mei Qi, Zhiyan Liu, Hongyan Dong, Xiying Zhang, Chunyan Zhai, Lei Xiang, Bo Han & Jinsong Li

  2. Department of Surgery, Jinan Central Hospital, Jinan, China

    Tao Lin

  3. Research Center for Medicinal Biotechnology, Shandong Academy of Medicinal Sciences, Jinan, China

    Lin Wang

  4. Department of Pathology, Linyi People’s Hospital, Linyi, China

    Hongyan Dong

  5. Department of Pathology, Shandong University Qilu Hospital, Jinan, China

    Zhiyan Liu, Yan Wang, Long Liu, Lei Xiang, Bo Han & Jinsong Li

  6. Department of Bone Surgery, Shandong University Qilu Hospital, Jinan, China

    Lei Qi

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  1. Ning Lu
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  2. Tao Lin
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  3. Lin Wang
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  9. Yan Wang
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  10. Long Liu
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  11. Lei Xiang
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  13. Bo Han
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  14. Jinsong Li
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Corresponding authors

Correspondence to Bo Han or Jinsong Li.

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Supplementary Fig. 1

Comparison of SOX4 IHC staining between chondrosarcoma and chondroma, ×400. (a) Representative IHC image of SOX4 in chondroma. (b) Representative IHC image of SOX4 in chondrosarcoma (GIF 150 kb)

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Lu, N., Lin, T., Wang, L. et al. Association of SOX4 regulated by tumor suppressor miR-30a with poor prognosis in low-grade chondrosarcoma. Tumor Biol. 36, 3843–3852 (2015). https://doi.org/10.1007/s13277-014-3026-2

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  • DOI: https://doi.org/10.1007/s13277-014-3026-2

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