MicroRNAs及其在泌尿系肿瘤的研究进展

microRNAs（miRNAs）是一类分布十分广泛的内源性非编码RNA,在动物、植物、病毒中广泛存在。miRNAs与肿瘤的发生发展预后有关,并在肿瘤的增殖、分化及调亡等方面有重要的作用。结合最近相关文献,本文就miRNAs与泌尿系肿瘤方面的进展作简要概述。     

基于 TCGA 数据库筛选、 分析并验证宫颈癌生物标志物

目的 基于生物信息学筛选分析宫颈癌差异表达基因 ( differentially expressed gene, DEGs) 及差 异表达 miRNA, 并进一步对差异基因和蛋白进行验证, 以期寻找潜在的生物标志物和治疗靶点。 方法 从 肿瘤基因组图谱 (the cancer genome atlas, TCGA) 数据库获取宫颈癌相关数据, edgeR 算法筛选 DEGs 和差 异 miRNAs。 利用 Cytoscape3. 8. 2 软件构建 mRNA-miRNA 共表达网络。 利用 DAVID 软件对 DEGs 和通过 miRWalk 网站预测的差异 miRNA 的目标基因进行 GO 富集分析和 KEGG 富集分析。 利用 qPCR 和 Western 印 迹技术对 DEGs 进行进一步验证。 结果 筛选出 149 个上调的 DEGs 和 171 个下调的 DEGs, 以及 46 个上调 的差异 miRNAs 和 64 个下调的差异 miRNAs。 DEGs 和 miRNA 目标基因在细胞组成上的富集具有一致性, 都富集在胞质、 核和核质中。 但共表达网络发现 DEGs 和差异 miRNAs 之间不存在明显的调控关系。 因此, 后续实验重点放在了对 DEGs 的验证上, 对差异表达性较为显著的 TCEAL6、 CLEC3B、 LMOD1、 CNN1 进行 了验证。 qPCR 显示它们在宫颈癌中表达量均显著降低, 符合预期, 对 CNN1 进行的 Western 印迹也显示其 在宫颈癌中的低表达。 结论 TCEAL6、 CLEC3B、 LMOD1、 CNN1 在宫颈癌中均显著低表达, 有望成为宫颈 癌生物标志物。     

Epigenome Modulation Induced by Ketogenic Diets

Ketogenic diets (KD) are dietary strategies low in carbohydrates, normal in protein, and high, normal, or reduced in fat with or without (Very Low-Calories Ketogenic Diet, VLCKD) a reduced caloric intake. KDs have been shown to be useful in the treatment of obesity, metabolic diseases and related disorders, neurological diseases, and various pathological conditions such as cancer, nonalcoholic liver disease, and chronic pain. Several studies have investigated the intracellular metabolic pathways that contribute to the beneficial effects of these diets. Although epigenetic changes are among the most important determinants of an organism’s ability to adapt to environmental changes, data on the epigenetic changes associated with these dietary pathways are still limited. This review provides an overview of the major epigenetic changes associated with KDs.     

肿瘤干细胞与肿瘤靶向治疗

肿瘤干细胞(TSC)理论认为,肿瘤内部存在的一小部分具有干细胞特性的细胞,是肿瘤形成、生长、转移和复发的根源,只有靶向肿瘤干细胞的治疗才能使恶性肿瘤治愈.目前肿瘤的治疗只能杀死大部分已分化的肿瘤细胞,不能杀死肿瘤干细胞,造成了肿瘤治疗效果的不理想.扰乱维持肿瘤干细胞自我更新的信号通路和微环境;或诱导肿瘤干细胞的分化;或针对肿瘤干细胞所表达的区别于正常干细胞的表面标志的靶向治疗都是可行的策略.     

小鼠肾脏缺血-再灌注损伤miRNAs差异表达谱研究

目的  筛选小鼠肾脏缺血-再灌注损伤（IRI）差异性表达的微小核糖核酸（miRNAs）,为进一步深入阐明肾脏IRI发生、发展的分子机制奠定基础。方法  应用微型动脉夹夹闭小鼠双侧肾动脉制备急性肾缺血损伤模型,将15只小鼠分为IRI组和假手术组（E组）,IRI组再分为A组（缺血时间45 min,再灌注时间24 h）、B组（缺血时间25 min,再灌注时间24 h）、C组（缺血时间45 min,再灌注时间4 h）、D组（缺血时间25 min,再灌注时间4 h）,每组3只。采用肾脏组织形态学改变和肾功能评估结果来鉴定各组小鼠的IRI程度;采用miRNAs芯片聚类分析对小鼠IRI特定缺血时间（25、45 min）和再灌注时间（4、24 h）下肾脏差异性表达差异表达的miRNAs进行筛选鉴定;采用实时定量逆转录-聚合酶链反应（qRT-PCR）对小鼠IRI后差异表达miRNAs芯片miR-695与miR-145进行验证。结果  肾脏组织形态学改变和肾功能评估结果显示成功建立IRI模型。与假手术组相比,肾脏IRI组共检出71种差异性表达显著的miRNAs,其中30种下调表达,41种上调表达。qRT-PCR法检测结果表明,以E组特定miRNAs的表达量标准化为1,miR-695及miR-145在肾脏IRI组的相对表达量分别为11.82和0.31（均为P＜0.05）,与芯片结果基本一致。结论  肾脏IRI后,miRNAs表达谱发生差异性改变,这些差异性表达的miRNAs将可作为肾脏IRI的分子标志物而具有潜在的临床及科研应用价值。     

Emerging Themes from EBV and KSHV microRNA Targets

EBV and KSHV are both gamma-herpesviruses which express multiple viral microRNAs. Various methods have been used to investigate the functions of these microRNAs, largely through identification of microRNA target genes. Surprisingly, these related viruses do not share significant sequence homology in their microRNAs. A number of reports have described functions of EBV and KSHV microRNA targets, however only three experimentally validated target genes have been shown to be targeted by microRNAs from both viruses. More sensitive methods to identify microRNA targets have predicted approximately 60% of host targets could be shared by EBV and KSHV microRNAs, but by targeting different sequences in the host targets. In this review, we explore the similarities of microRNA functions and targets of these related viruses.     

MicroRNA-Mediated Restriction of HIV-1 in Resting CD4+ T Cells and Monocytes

In contrast to activated CD4⁺ T cells and differentiated macrophages, resting CD4⁺ T cells and monocytes are non-permissive for HIV-1 replication. The mediators which regulate the resting or quiescent phenotype are often actively involved in the restriction of viral replication and the establishment and maintenance of viral latency. Recently, certain microRNAs which are highly expressed in resting cells have been implicated in this capacity, inhibiting the expression of cellular proteins that are also viral co-factors; following activation these microRNAs exhibit decreased expression, while their targets are correspondingly up-regulated, contributing to a favorable milieu for virus replication. Other microRNAs exhibiting a similar expression pattern in resting and activated cells have been shown to directly target the HIV-1 genome. In this review we will discuss the resting state and the causes behind viral restriction in resting cells, with emphasis on the role of microRNAs.