The type 1 diabetes resistance locus B10 Idd9.3 mediates impaired B‐cell lymphopoiesis and implicates microRNA‐34a in diabetes protection

NOD.B10 Idd9.3 mice are congenic for the insulin‐dependent diabetes (Idd) Idd9.3 locus, which confers significant type 1 diabetes (T1D) protection and encodes 19 genes, including microRNA (miR)‐34a, from T1D‐resistant C57BL/10 mice. B cells have been shown to play a critical role in the priming of autoantigen‐specific CD4⁺ T cells in T1D pathogenesis in non‐obese diabetic (NOD) mice. We show that early B‐cell development is impaired in NOD.B10 Idd9.3 mice, resulting in the profound reduction of transitional and mature splenic B cells as compared with NOD mice. Molecular analysis revealed that miR‐34a expression was significantly higher in B‐cell progenitors and marginal zone B cells from NOD.B10 Idd9.3 mice than in NOD mice. Furthermore, miR‐34a expression in these cell populations inversely correlated with levels of Foxp1, an essential regulator of B‐cell lymphopoiesis, which is directly repressed by miR‐34a. In addition, we show that islet‐specific CD4⁺ T cells proliferated inefficiently when primed by NOD.B10 Idd9.3 B cells in vitro or in response to endogenous autoantigen in NOD.B10 Idd9.3 mice. Thus, Idd9.3‐encoded miR‐34a is a likely candidate in negatively regulating B‐cell lymphopoiesis, which may contribute to inefficient expansion of islet‐specific CD4⁺ T cells and to T1D protection in NOD.B10 Idd9.3 mice.     

非综合征性唇腭裂患者四例microRNA的表达分析

目的寻找可能导致非综合征性唇腭裂的microRNA。方法采用丹麦Exiqon公司microRNA基因芯片技术对4例非综合征性唇腭裂患者的唇腭组织与4例正常胎儿的脐带组织进行检测比对。结果实验组（唇腭裂患儿组）与对照组（正常胎儿组）出现差异表达的microRNA共254条,其中实验组较对照组表达上调的181条,表达下调的73条。结论差异表达较显著的microRNA可能与非综合征性唇腭裂的发生存在关联。     

microRNA调控间充质干细胞成骨分化的研究进展

间充质干细胞是一类体内广泛存在的多能干细胞,具有多向分化潜能,为多种组织器官提供保护及损伤修复。近年来,间充质干细胞向成骨细胞诱导分化用于治疗骨代谢等相关性疾病已成为热点。microRNA（miRNA）作为生物体内重要的小分子非编码RNA,通过转录后调控影响基因表达,参与各种生命过程。研究显示,多种不同的miRNA在间充质干细胞向成骨分化过程中起着核心调节作用。本文结合相关文献,对miRNA调控间充质干细胞成骨分化的作用及机制归纳总结,以帮助全面了解靶向miRNA治疗骨代谢性相关疾病的潜能。     

小鼠牙周炎模型牙周组织中MicroRNA表达谱研究

目的：建立小鼠牙周炎模型牙周组织和正常小鼠牙龈组织microRNA表达差异谱,为探讨microRNA在牙周炎发病过程中是否起到可能的调控作用提供前期研究基础。方法：小鼠牙周炎牙周组织和正常小鼠牙龈组织各3例,Trizol法抽提细胞总RNA。采用基因芯片技术,将总RNA与microRNA芯片杂交,GenePixProV6．0软件进行数据分析。结果：与正常小鼠牙龈组织相比,牙周炎小鼠牙周组织中表达上调超过2倍的microRNA有4个,分别为mmu—miR-126,mmu—miR-32,mmu—miR-147,mmu—miR-155。其中牙周炎小鼠牙周组织中mmu—miR-155表达量明显提高,是正常小鼠牙龈组织的5．2倍。结论：筛选出的差异表达microRNA可能参与了牙周炎的发病过程,为探讨microRNA分子在牙周炎中的可能作用提供了途径。     

Altered microRNA expression profile with miR-27b down-regulation correlated with disease activity of oral lichen planus

Oral Diseases (2012) 18 , 265–270 Background: Increasing evidence indicates that microRNAs (miRNAs) play a vital role in the pathogenesis of inflammatory and autoimmune diseases. The objective of this study was to investigate the altered miRNA expression profile in patients with oral lichen planus (OLP) and determine the miR‐27b expression. Methods: We compared miRNA expression patterns in oral biopsy specimens from patients with OLP (n = 3) with those from normal controls (n = 3) using microarray technology. We further assessed the miR‐27b expression in specimens from patients with OLP (n = 53) against controls (n = 34) using real‐time quantitative PCR (RT‐QPCR), and miR‐27b expression in specimens from patients with OLP (n = 15) against controls (n = 12) using in situ hybridization (ISH). Results: Using microarray analysis, a total of 46 differentially expressed miRNAs with more than 2‐fold change were identified, including 8 up‐regulated and 38 down‐regulated miRNAs. Both RT‐QPCR and ISH analyses revealed that miR‐27b was significantly down‐regulated in OLP tissue, and miR‐27b expression was even more suppressed in atrophic‐erosive OLP than in reticular OLP. In addition, miR‐27b was found to be expressed in the epithelial keratinocyte layer of both normal and OLP tissues. Conclusion: These data indicate that miRNAs may be the novel candidate biomarkers for the implication of miRNAs in the pathogenesis of OLP.     

Epigenetic studies of suicidal behavior

Recent studies have shown an association between gene alterations by epigenetic mechanisms and suicidal behavior. These epigenetic mechanisms are mitotically, and in some cases meiotically, heritable changes in the genome through non-DNA sequence coding processes that alter gene expression as a result of variable changes in environmental stimuli. Genome-wide association studies have been inconsistent in elucidating the association between genes and suicidal behavior, thereby making the heritability of suicidal behavior is unclear. However, recent epigenetic studies have provided evidence that epigenetic mechanisms could deliver the missing link between the heritability of suicidal behavior and the interaction between environment and the genome. The present review provides an in-depth discussion of epigenetic mechanisms that may regulate gene expression in suicidal behavior. The findings of current epigenetic studies on suicidal behavior will also be discussed considering future epigenome-wide association studies on elucidating the contributions of environment and genome on suicidal behavior.     

miR-451在胃癌组织中的表达及临床意义

目的观察miR-451在胃癌组织中的表达,并探讨其与胃癌相关临床因素的关系。方法收集18例胃癌患者的胃癌组织和胃癌旁组织,应用RT-PCR技术检测miR-451的表达水平(以U6为对照),并分析其与胃癌相关临床因素的关系。结果与胃癌旁组织相比,miR-451在胃癌组织中明显下调(P<0.05)。其中上调6例,下调12例,下调比率66.67%(12/18)。miR-451的表达水平与胃癌的分化相关(P<0.05),与年龄、性别、TNM分期、Borrmann分型、浸润深度、淋巴结转移等无明显相关。结论 miR-451在胃癌组织中低表达,并与胃癌的分化程度密切相关,表明其可能参与了胃癌的发生和发展过程。     

A variant in microRNA-196a2 is not associated with susceptibility to and progression of colorectal cancer in Chinese

Background: MicroRNAs (miRNAs) are small non‐coding RNAs with regulatory functions as tumour suppressors and oncogenes. Although single nucleotide polymorphism (SNP) in miRNA regions have been reported to be rare and unlikely to be functionally important, recent evidence suggested that rs11614913 SNP in miR‐196a2 was associated with the susceptibility of lung cancer, breast cancer, congenital heart disease and shortened survival time of non‐small‐cell lung cancer. Aims: The aim of this study was to investigate the association between this genetic variant and the risk and/or progression of colorectal cancer (CRC). Methods: A total of 126 CRC patients and 407 healthy controls was periodically enrolled. DNA was extracted from blood specimens, and miR‐196a2 polymorphism was genotyped by polymerase chain reaction–ligation detection reaction (PCR–LDR). Results: Although the frequency of CC homozygotes or miR‐196a2C allele‐containing genotypes (CT and CC) was lower in CRC patients than in the healthy controls, no significant association between miR‐196a2 polymorphism and the risk of CRC was found. The frequency of the ‘C’ allele in CRC patients was also not significantly lower than in healthy controls. In a subsequent analysis of the association between this polymorphism and the progression of CRC, there was still no significant difference in both genotype and allelic frequency. Conclusions: Our results suggest that miR‐196a2 polymorphism is not associated with both an increased risk and progression of CRC in Chinese.