ABSTRACT
@#[摘 要] 目的：探究含硬化蛋白域蛋白1（SOSTDC1）对宫颈癌细胞恶性生物学行为的调控及其分子机制。方法：收集2020年8月至2022年5月间在福建省肿瘤医院活检或手术切除的53例宫颈癌组织和相应的癌旁组织标本，免疫组化法检测SOSTDC1蛋白在宫颈癌组织及相应癌旁组织中的表达，qPCR法检测正常宫颈细胞、宫颈癌细胞中SOSTDC1 mRNA表达；将SOSTDC1过表达慢病毒（OE-sostdc1）和对照空病毒（NC）感染宫颈癌细胞SiHa及CaSki，将其分为SiHa-OE-sostdc1、SiHa-NC、CaSki-OE-sostdc1、CaSki-NC组，采用WST-1法、细胞集落形成实验、Transwell实验和WB法检测转染各组SiHa及CaSki细胞的增殖、集落形成、迁移和侵袭能力和BMP、Wnt/β-catenin信号途径相关蛋白及上皮-间充质转化（EMT）相关蛋白的表达。用DNA甲基化酶抑制剂5-氮杂2'-脱氧胞苷（5'-Aza-CdR）处理宫颈癌细胞后采用qPCR和WB法检测SOSTDC1 mRNA及蛋白的表达变化，用甲基化特异性PCR（MSP）检测5例配对宫颈癌组织与癌旁组织中SOSTDC1基因启动子区甲基化水平，同时qPCR检测其SOSTDC1 mRNA水平。结果：与癌旁组织比较，SOSTDC1蛋白在宫颈癌组织中呈低表达（P<0.01），且与淋巴结转移与FIGO分期有关联（均P<0.05）；与正常宫颈HUCEC细胞比较，SOSTDC1 mRNA在宫颈癌C33A、HeLa、SiHa、CaSki细胞中均呈低表达（均P<0.01）。过表达SOSTDC1显著抑制SiHa及CaSki细胞的增殖、迁移和侵袭能力（均P<0.05）。WB法结果检测显示，过表达SOSTDC1显著抑制SiHa及CaSki细胞中磷酸化Smad、Dvl2/3、β-catenin、VIM、N-cadherin、Snail蛋白的表达（均P<0.05），5'-Aza-CdR处理后的SiHa及CaSki细胞中SOSTDC1 mRNA和蛋白水平均显著增加（均P<0.05），MSP检测结果显示，相较于癌旁组织，宫颈癌组织中SOSTDC1基因启动子区呈高度甲基化，且SOSTDC1 mRNA水平降低（P<0.01）。结论：SOSTDC1在宫颈癌组织中呈低表达且与肿瘤的恶性进展关联，其表达下调与其基因启动子区高度甲基化有关，过表达SOSTDC1可能通过阻断BMP及Wnt/β-catenin信号通路从而抑制SiHa、CaSki细胞的增殖、侵袭和迁移能力。
ABSTRACT
OBJECTIVES: Clinically, patients with chronic heart failure arising from different etiologies receive the same treatment. However, the prognoses of these patients differ. The purpose of this study was to elucidate whether the pathogenesis of heart failure arising from different etiologies differs. METHODS: Heart failure-related dataset GSE1145 was obtained from the Gene Expression Omnibus database. Differentially expressed genes were identified using R. A protein-protein interaction network of the differentially expressed genes was constructed using Search Tool for the Retrieval of Interacting Genes. The modules in each network were analyzed by Molecular Complex Detection of Cytoscape. The Database for Annotation, Visualization and Integrated Discovery was used to obtain the functions of the modules. RESULTS: Samples contained in GSE1145 were myocardial tissues from patients with dilated cardiomyopathy, familial cardiomyopathy, hypertrophic cardiomyopathy, ischemic cardiomyopathy, and post-partum cardiomyopathy. The differentially expressed genes, modules, and functions of the modules associated with different etiologies varied. Abnormal formation of extracellular matrix was overlapping among five etiologies. The change in cytoskeleton organization was specifically detected in dilated cardiomyopathy. The activation of the Wnt receptor signaling pathway was limited to hypertrophic cardiomyopathy. The change in nucleosome and chromatin assembly was associated with only familial cardiomyopathy. Germ cell migration and disrupted cellular calcium ion homeostasis were solely detected in ischemic cardiomyopathy. The change in the metabolic process of glucose and triglyceride was detected in only post-partum cardiomyopathy. CONCLUSION: These results indicate that the pathogenesis of heart failure arising from different etiologies varies, which may provide molecular evidence supporting etiology-based treatment for heart failure patients.