4.1 Article

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

Journal

TUMOR BIOLOGY
Volume 35, Issue 9, Pages 9053-9059

Publisher

SPRINGER
DOI: 10.1007/s13277-014-1974-1

Keywords

TPM3; MMP-9; SNAI1; Invasion; Migration; EMT; Survival; Glioma

Categories

Funding

  1. National High Technology Research and Development Program of China (863) [2012AA02A508]
  2. International Cooperation Program [2012DFA30470]
  3. National Natural Science Foundation of China [91229121, 81272792, 81172389, 81372709, 81302185, 81101901, 81302184]
  4. Jiangsu Province's Natural Science Foundation [BK2011847, 20131019]
  5. Jiangsu Province's Key Provincial Talents Program [RC2011051]
  6. Jiangsu Province's Key Discipline of Medicine [XK201117]
  7. Jiangsu Provincial Special Program of Medical Science [BL2012028]
  8. Program for Development of Innovative Research Team in the First Affiliated Hospital of NJMU
  9. Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)

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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.

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