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.     

Construction of miRNA-mRNA network reveals crucial miRNAs and genes in acute myocardial infarction

Acute myocardial infarction (AMI) is a severe cardiovascular disease. This study aimed to identify crucial microRNAs (miRNAs) and mRNAs in AMI by establishing a miRNA-mRNA network. The microarray datasets GSE31568, GSE148153, and GSE66360 were downloaded from the Gene Expression Omnibus (GEO) database. We identified differentially expressed miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) in AMI samples compared with normal control samples. The consistently changing miRNAs in both GSE31568 and GSE148153 datasets were selected as candidate DE-miRNAs. The interactions between the candidate DE-miRNAs and DE-mRNAs were analyzed, and a miRNA-mRNA network and a protein-protein interaction network were constructed, along with functional enrichment and pathway analyses. A total of 209 DE-miRNAs in the GSE31568 dataset, 857 DE-miRNAs in the GSE148153 dataset, and 351 DE-mRNAs in the GSE66360 dataset were identified. Eighteen candidate DE-miRNAs were selected from both the GSE31568 and GSE148153 datasets. Furthermore, miR-646, miR-127-5p, miR-509-5p, miR-509-3-5p, and miR-767-5p were shown to have a higher degree in the miRNA-mRNA network. THBS-1 as well as FOS was a hub gene in the miRNA-mRNA network and the protein-protein interaction (PPI) network, respectively. CDKN1A was important in both miRNA-mRNA network and PPI network. We established a miRNA-mRNA network in AMI and identified five miRNAs and three genes, which might be used as biomarkers and potential therapeutic targets for patients with AMI.     

疟原虫表观遗传学研究进展

疟原虫的生活史包括配子体、裂殖子、环状体等多个阶段,先后寄生在多种类型的宿主细胞才完成完整的生命周期。在这些生活史中的不同虫期,疟原虫表现出明显的表型差异;在应对生存环境的改变时,其基因表达能够很精确地做出应对。近年来诸多研究表明,无论是这些生命阶段的转换,还是对宿主的适应,疟原虫表观遗传学方面的调控都起了很大的作用。对疟原虫表观遗传学的研究,有利于深入了解疟原虫与宿主的相互作用机制,对防治疟疾工作具有重要意义。本文从组蛋白修饰、DNA甲基化、非编码RNA编辑等方面介绍目前疟原虫表观遗传学研究进展。     

miR-182在人乳腺癌中的表达及意义

目的 探讨miR-182在人乳腺良恶性组织和细胞株中的表达及其意义.方法 采用实时荧光定量PCR法检测miR-182在2株正常人乳腺细胞、9株人乳腺癌细胞(包括5株低度恶性、4株高度恶性)、11例临床乳腺良性病变组织和22例乳腺癌组织中的表达.结果 乳腺癌细胞株miR-182表达显著低于正常乳腺上皮细胞株,而在高度恶性...     

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.