Tao Tao, Shi Yan, Han Dongfeng, Luan Wenkang, Qian Jin, Zhang Junxia, Wang Yingyi, You Yongping
Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Tumour Biol. 2014 Sep;35(9):9053-9. doi: 10.1007/s13277-014-1974-1. Epub 2014 Jun 10.
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.
最近的研究表明,许多分子机制,如表皮生长因子受体(EGFR)、蛋白激酶B(AKT)、信号转导和转录激活因子3(STAT3)以及β-连环蛋白信号通路,都与胶质瘤有关。然而,该疾病的预后仍然很差。探索胶质瘤的潜在机制以及鉴定早期诊断和准确预后的有效标志物在当今仍然很重要。在本研究中,我们采用生存分析确定肌动蛋白3(TPM3)过表达与高级别胶质瘤及更高的死亡率显著相关。通过基因芯片结合Pearson相关性分析,我们发现TPM3与基质金属蛋白酶(MMP)家族成员及上皮-间质转化(EMT)样激活因子的表达呈正相关。降低TPM3(通过TPM3小干扰RNA)可抑制胶质瘤细胞的侵袭和迁移,并降低MMP-9和SNAI1的水平。据我们所知,我们的工作首次表明TPM3在胶质瘤进展中起关键作用,并为MMP家族成员及EMT样激活因子在介导TPM3功能信号调控胶质瘤中的关键作用提供了新的见解。