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Tumor Biology

, Volume 35, Issue 9, pp 9053–9059 | Cite as

TPM3, a strong prognosis predictor, is involved in malignant progression through MMP family members and EMT-like activators in gliomas

  • Tao Tao
  • Yan Shi
  • Dongfeng Han
  • Wenkang Luan
  • Jin Qian
  • Junxia Zhang
  • Yingyi Wang
  • Yongping You
  • Chinese Glioma Cooperative Group (CGCG)
Research Article

Abstract

Recent studies have shown that many molecular mechanisms, such as the EGFR, AKT, STAT3, and beta-catenin pathways, are involved in glioma. However, the prognosis of the disease remains poor. Explorations of the underlying mechanisms of glioma and identification of effective markers for early diagnosis and accurate prognostication remain important today. In this study, we employed survival analysis to determine that TPM3 overexpression was significantly associated with high-grade gliomas and higher mortality. Using microarray combined with Pearson correlation analysis, we found that TPM3 was positively correlated with the expression of MMP family members and EMT-like activators. Reduction of TPM3 (via TPM3-siRNA) inhibited cellular invasion and migration and decreased MMP-9 and SNAI1 levels in glioma cells. To the best of our knowledge, our work is the first to show that TPM3 plays a critical role in the progression of gliomas and provides novel insights into the key roles of MMP family members and EMT-like activators that mediate TPM3 functional signaling for glioma regulation.

Keywords

TPM3 MMP-9 SNAI1 Invasion Migration EMT Survival Glioma 

Notes

Acknowledgments

This work was supported by grants from the National High Technology Research and Development Program of China (863) (2012AA02A508), International Cooperation Program (2012DFA30470), National Natural Science Foundation of China (91229121, 81272792, 81172389,81372709, 81302185, 81101901,81302184), Jiangsu Province’s Natural Science Foundation (BK2011847 and 20131019), Jiangsu Province’s Key Provincial Talents Program (RC2011051), Jiangsu Province’s Key Discipline of Medicine (XK201117), Jiangsu Provincial Special Program of Medical Science (BL2012028), and Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Conflicts of interest

None

Supplementary material

13277_2014_1974_Fig6_ESM.gif (13 kb)
Supplementary Fig.1

Cell proliferation determined by CCK-8 assay. (A and B) CCK-8 assays showed that there was no significant difference between si-TPM3-transfected cells and negative control group within 24 hours. #P > 0.05. Results were presented as mean±SD from three independent experiments. (GIF 12 kb)

13277_2014_1974_MOESM1_ESM.tif (1.7 mb)
High resolution image (TIFF 1740 kb)
13277_2014_1974_Fig7_ESM.gif (94 kb)
Supplementary Fig.2

MMP-9 and SNAI1 involved in TPM3 functional signaling for glioma invasion and migration. (A and B) si-MMP9 and si-SNAI1 were introduced into TPM3-treated cells. Decreased MMP9 or SNAI1 in TPM3-treated cells rescued the invasion phenotype induced by TPM3. (C and D) Introduction of si-MMP9 or si-SNAI1 abrogated TPM3 overexpression-induced cellular migration. (*P < 0.05, **P < 0.01). Results were presented as mean±SD from three independent experiments. (GIF 93 kb)

13277_2014_1974_MOESM2_ESM.tif (1.7 mb)
High resolution image (TIFF 1691 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Tao Tao
    • 1
    • 2
  • Yan Shi
    • 1
  • Dongfeng Han
    • 1
  • Wenkang Luan
    • 1
  • Jin Qian
    • 1
    • 3
  • Junxia Zhang
    • 1
  • Yingyi Wang
    • 1
  • Yongping You
    • 1
  • Chinese Glioma Cooperative Group (CGCG)
  1. 1.Department of NeurosurgeryFirst Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Surgical Research Center, Medical SchoolSoutheast UniversityNanjingChina
  3. 3.Department of NeurosurgeryPeople’s Hospital of Xuancheng CityAnhuiChina

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