siRNA介导的间皮沉默治疗间皮瘤

众所周知，间皮素（MSLN）在某些癌症中过表达，并且它通过Wnt家族成员1蛋白在细胞生长中起作用。恶性转化通常是随着自噬相关基因自动调节的破坏而发生的。我们检查了MSLN对间皮瘤病例中生存和临床病理学特征的影响，以及与间皮瘤细胞系中siRNA介导的MSLN沉默转染后与自噬，侵袭，凋亡相关基因相关的基因的变化（SPC212）。通过免疫组织化学分析了MSLN的表达，在福尔马林固定的石蜡包裹的60例间皮瘤病例中。MSLN表达通过中位MSLN Histoscores分类为低（L），高（H）。在间皮瘤病例中确定了MSLN表达水平，临床病理特征和存活之间的相关性。转染siRNA介导的MSLN孵育的SPC212细胞并将其与阴性对照siRNA进行比较。确定MRNA水平用于与RT-PCR的自噬，侵袭和凋亡相关的基因，以及在MSLN沉默后SPC212细胞中的蛋白质印迹。所有病例对MSLN表达均具有免疫反应性。根据Kaplan-Meier的生存分析，H-MSLN与有利的预后有关，但Cox回归分析表明，仅阶段是估计生存率的重要独立因素。 MSLN overexpression was significantly higher in early-stage, mesothelioma cases without nodal involvement. Significant silencing in MSLN was found (87.5%) after siRNA applications. Apoptosis and autophagy were upregulated by increasing apoptosis-related genes, BAK1, BAX, CASP1-7, and autophagy-related genes, ATG2, ATG16L1. Cell proliferation was knocked down predominantly by inhibiting the invasion-related genes, MMP1, 10, 11, 13, in SPC212 cell lines. MSLN silencing was determined to significantly increase CASP3, but did not change LC3 in western blotting, respectively. In conclusion, siRNA-mediated silencing MSLN can promote apoptosis, autophagy, and also partially inhibit proliferation. We suggest that MSLN can serve as a potential therapeutic target in mesothelioma.