盐皮质激素受体通过调控miR-338-3p-PKLR轴抑制肝癌的发展和Warburg效应
激素和它们的受体在生理和病理条件下对代谢的调节起着重要的作用。我们在4株肝癌细胞用siRNA的方法筛选20种激素受体对肝癌细胞的瓦伯格效应（Warburg effect）尤其是乳酸产生的影响。我们发现很多受体的siRNA都影响乳酸的产生。其中盐皮质激素受体(mineralocorticoid receptor, MR) 的siRNA在4株肝癌细胞都表现出增加乳酸的产生。体外和体内实验表明MR影响细胞增殖、细胞周期和凋亡。进一步的机制研究揭示，作为一个转录因子，MR直接调节miR-338-3p的表达，而miR-338-3p又通过靶基因PKLR(pyruvate kinase, liver and red blood，糖酵解途径的关键酶)来抑制肝癌细胞的瓦伯格效应。另外，与癌旁组织相比，有81%的肝癌病人的肝癌组织中MR的表达都发生下调。这种下调是由MR的染色体缺失和去乙酰化引起的。在肿瘤组织中，MR的低表达和病人的预后差相关；miR-338-3p的表达和MR的表达水平呈正相关，和PKLR的表达呈负相关。结论：我们的研究首次揭示了MR通过miR-338-3p/PKLR这个途径抑制肝癌的瓦伯格效应。
PKI Mantra Intro 2015
The Mantra™ quantitative pathology workstation lets you visualize, quantify, and phenotype multiple types of immune cells simultaneously in intact FFPE tissue sections for cancer immunology research. Mantra allows you to maintain tissue morphology to help better understand the types and roles of cells within the tumor and tumor microenvironment. The system comes with powerful inForm® Tissue Finder™ advanced image analysis software that features user-trainable algorithms for automatic recognition of specific tissue and cell types, as well as per-cell analysis of biomarker expression and phenotyping to differentiate among cell types. Pathology Views™ creates familiar-looking brightfield (H&E, DAB, hematoxylin) renderings from original multi-label fluorescence images. PerkinElmer’s cancer immunology workflow has been validated using Opal™ reagent kits. Opal methodology enables specific staining of multiple tissue biomarkers reaching up to 6-plex and beyond in a single tissue section. Learn more: http://www.perkinelmer.com/catalog/pr...