Xu Caihua, Hua Fei, Chen Yihuan, Huang Haoyue, Ye Wenxue, Yu Yunsheng, Shen Zhenya
Department of Cardiovascular Surgery of the First Affiliated Hospital and Institute for Cardiovascular Science, Soochow University, Suzhou, 215000, China.
J Exp Clin Cancer Res. 2015 Dec 21;34:151. doi: 10.1186/s13046-015-0269-8.
Metastasis-associated gene 1(MTA1) has been identified as an oncogene in many tumors, and aberrant MTA1 expression has been linked to carcinogenesis and metastasis. We aim to investigate the mechanism of MTA1 and metastasis in malignant pleural mesothelioma (MPM).
Real-time polymerase chain reaction (PCR) and immunohistochemical staining were employed to detect MTA1 and E-cadherin expression in MPM tissues and corresponding adjacent tissues. Stable clone with knock-down of MTA1 was generated with shRNA via lentivirus technology in MPM cell lines. Wound-healing assay, transwell assay and PCR array were carried out for detecting invasion and migration of MPM cells. Luciferase reporter assay was performed to validate the effect of MTA1 on E-cadherin.
MTA1 expression is up-regulated in MPM and shown a negative correlation with E-cadherin expression. MTA1 could enhance the invasion and migration of MPM cells via suppressing the expression of E-cadherin. MTA1 overexpression is associated with pathology, metastasis and survival rate of MPM patients.
MTA1 plays an important role in Epithelial-to-mesenchymal transition (EMT) to promote metastasis via suppressing E-cadherin expression, resulting in a poor prognosis in MPM. MTA1 is a novel biomarker and indicative of a poor prognosis in MPM patients.
转移相关基因1(MTA1)在许多肿瘤中被鉴定为癌基因,MTA1表达异常与肿瘤发生和转移有关。我们旨在研究MTA1在恶性胸膜间皮瘤(MPM)中的作用机制及其与转移的关系。
采用实时聚合酶链反应(PCR)和免疫组化染色检测MPM组织及相应癌旁组织中MTA1和E-钙黏蛋白的表达。通过慢病毒技术将shRNA转染至MPM细胞系中,构建MTA1基因敲低的稳定克隆。采用划痕实验、Transwell实验及PCR芯片检测MPM细胞的侵袭和迁移能力。利用荧光素酶报告基因实验验证MTA1对E-钙黏蛋白的影响。
MPM组织中MTA1表达上调,且与E-钙黏蛋白表达呈负相关。MTA1可通过抑制E-钙黏蛋白的表达增强MPM细胞的侵袭和迁移能力。MTA1过表达与MPM患者的病理类型、转移及生存率相关。
MTA1通过抑制E-钙黏蛋白的表达在上皮-间质转化(EMT)中发挥重要作用,促进MPM转移,导致患者预后不良。MTA1是一种新的生物标志物,提示MPM患者预后不良。