Tumor Biology

, Volume 36, Issue 5, pp 3843–3852 | Cite as

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

  • Ning Lu
  • Tao Lin
  • Lin Wang
  • Mei Qi
  • Zhiyan Liu
  • Hongyan Dong
  • Xiying Zhang
  • Chunyan Zhai
  • Yan Wang
  • Long Liu
  • Lei Xiang
  • Lei Qi
  • Bo Han
  • Jinsong Li
Research Article

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.

Keywords

SOX4 miR-30a Chondrosarcoma Prognosis 

Notes

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).

Conflicts of interest

None

Supplementary material

13277_2014_3026_Fig7_ESM.gif (151 kb)
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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High resolution image (TIFF 5256 kb)
13277_2014_3026_MOESM2_ESM.doc (37 kb)
ESM 2 (DOC 37 kb)
13277_2014_3026_MOESM3_ESM.doc (34 kb)
ESM 3 (DOC 34 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Ning Lu
    • 1
  • Tao Lin
    • 2
  • Lin Wang
    • 1
    • 3
  • Mei Qi
    • 1
  • Zhiyan Liu
    • 1
    • 5
  • Hongyan Dong
    • 1
    • 4
  • Xiying Zhang
    • 1
  • Chunyan Zhai
    • 1
  • Yan Wang
    • 5
  • Long Liu
    • 5
  • Lei Xiang
    • 1
    • 5
  • Lei Qi
    • 6
  • Bo Han
    • 1
    • 5
  • Jinsong Li
    • 1
    • 5
  1. 1.Department of PathologyShandong University Medical SchoolJinanChina
  2. 2.Department of SurgeryJinan Central HospitalJinanChina
  3. 3.Research Center for Medicinal BiotechnologyShandong Academy of Medicinal SciencesJinanChina
  4. 4.Department of PathologyLinyi People’s HospitalLinyiChina
  5. 5.Department of PathologyShandong University Qilu HospitalJinanChina
  6. 6.Department of Bone SurgeryShandong University Qilu HospitalJinanChina

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