Variance in the identification of microRNAs deregulated in Alzheimer's disease and possible role of lincRNAs in the pathology: The need of larger datasets

Non-coding RNAs, such as microRNAs and long non-coding RNAs, represent the next major step in understanding the complexity of gene regulation and expression. In the past decade, tremendous efforts have been put mainly into identifying microRNAs that are changed in Alzheimer's disease, with the goal to provide biomarkers of the disease and to better characterize molecular pathways that are deregulated concomitantly to the formation of Tau and amyloid aggregates. This review underlines the importance of correctly defining, in a deluge of high-throughput data, which microRNAs are abnormally expressed in Alzheimer's disease patients. Despite a clear lack of consensus on the topic, miR-132 is emerging as a neuronal microRNA being gradually down-regulated during disease and showing important roles in the maintenance of brain integrity. Insight into the biological importance of other classes of non-coding RNAs also rapidly increased over the last years and therefore we discuss the possible implication of long non-coding RNAs in Alzheimer's disease.     

MicroRNAs in human skin ageing

The skin protects humans from the surrounding environment. Tissues undergo continuous renewal throughout an individual's lifetime; however, there is a decline in the regenerative potential of tissue with age. The accumulation of senescent cells over time probably reduces tissue regenerative capacity and contributes to the physiological ageing of the tissue itself. The mechanisms that govern ageing remain unclear and are under intense investigation, and insight could be gained by studying the mechanisms involved in cellular senescence. In vitro, keratinocytes and dermal fibroblasts undergo senescence in response to multiple cellular stresses, including the overproduction of reactive oxygen species and the shortening of telomeres, or simply by reaching the end of their replicative potential (i.e., reaching replicative senescence). Recent findings demonstrate that microRNAs play key roles in regulating the balance between a cell's proliferative capacity and replicative senescence. Here, we will focus on the molecular mechanisms regulated by senescence-associated microRNAs and their validated targets in both keratinocytes and dermal fibroblasts.     

MicroRNA及其在黑素瘤中作用的新认识

MicroRNA（miRNA）是一类长约18—22个核苷酸的单链非编码小分子。在转录后水平参与调控靶基因的表达,其在细胞生长、增殖、代谢及肿瘤形成等一系列生物学过程中发挥重要作用。miRNA具有癌基因和,或抑癌基因的双重作用并具有组织特异性和时序特异性。miRNA的异常表达被认为与黑素瘤的发生发展密切相关。黑素瘤是严重危害患者健康和生命的疾病,其病死率高,晚期患者5年生存率〈5％,预后差。近几年来,其发病率逐年升高,年增长率约3％。本文试就miRNA的生物学特性及其在黑素瘤中作用的新进展、新认识作一综述。     

微小RNA-146a对类风湿关节炎患者滑膜成纤维细胞抑制作用的研究

目的 研究微小RNA-146a(miR-146a)对类风湿关节炎(RA)患者滑膜成纤维细胞增殖及细胞因子分泌的影响.方法 体外分离培养RA患者滑膜成纤维细胞,脂质体转染化学合成的miR-146a,~3H掺入法检测滑膜成纤维细胞增殖.酶联免疫吸附试验(ELISA)法检测细胞上清白细胞介素(IL)-8及IL-6水平.实时定量聚合酶链反应(PCR)检测滑膜成纤维细胞中miR-146a靶分子肿瘤坏死因子受体相关因子6(TRAF6)、IL-受体相关激酶(IRAKI)的mRNA水平.应用独立样本t检验进行统计学分析.结果 与阴性对照小RNA相比,miR-146a转染后的滑膜成纤维细胞增殖能力明显下降(2015±545与8799±1922,P<0.01),IL-8及IL-6分泌受到明显抑制[(153±49)pg/ml与(311±123)pg/ml,P<0.01和(295±95)pg/ml与(459±126)pg/ml,P<0.05].定量PCR检测IRAK1的mRNA水平显示,miR-146a转染可明显下调滑膜成纤维细胞IRAK1的表达(0.28±0.07与1,P<0.01).结论 miR-146a可能通过下调IRAKI表达,进而抑制滑膜成纤维细胞增殖及IL-8、IL-6等炎性细胞因子分泌,从而发挥抑制RA滑膜炎症的作用.     

Pathobiology of the neutrophil-intestinal epithelial cell interaction: role in carcinogenesis

The role of chronic inflammation,acting as an independent factor,on the onset of gastrointestinal carcinogenesis is now well accepted.However,even if there is an increase in the number of elements directly involving polymorphonuclear leukocytes (PMNL),as a major actor in digestive carcinogenesis,the different cellular and molecular events occurring in this process are still not completely understood.The transepithelial migration of PMNL,which is the ultimate step of the afflux of PMNL into the digestive mucosa,is a complex phenomenon involving sequential interaction of molecules expressed both on PMNL and on digestive epithelial cells.Chronic inflammatory areas rich in PMNL [so-called (chronic active inflammation)] and iterative transepithelial migration of PMNL certainly evoke intracellular signals,which lead toward progressive transformation of epithelia.Among these different signals,the mutagenic effect of reactive oxygen species and nitrates,the activation of the nuclear factor-κB pathway,and the modulation of expression of certain microRNA are key actors.Following the initiation of carcinogenesis,PMNL are involved in the progression and invasion of digestive carcinomas,with which they interact.It is noteworthy that different subpopulations of PMNL,which can have some opposite effects on tumor growth,in association with different levels of transforming growth factor-β and with the number of CD8 positive T lymphocytes,could be present during the development of digestive carcinoma.Other factors that involve PMNL,such as massive elastase release,and the production of angiogenic factors,can participate in the progression of neoplastic cells through tissues.PMNL may play a major role in the onset of metastases,since they allow the tumor cells to cross the endothelial barrier and to migrate into the blood stream.Finally,PMNL play a role,alone or in association with other cell parameters,in the initiation,promotion,progression and dissemination of digestive carcinomas.This review focuses on the main currently acc     

Macro-management of microRNAs in cell cycle progression of tumor cells and its implications in anti-cancer therapy

The cell cycle, which is precisely controlled by a number of regulators, including cyclins and cyclin-dependent kinases (CDKs), is crucial for the life cycle of mammals. Cell cycle dysregulation is implicated in many diseases, including cancer. Recently, compelling evidence has been found that microRNAs play important roles in the regulation of cell cycle progression by modulating the expression of cyclins, CDKs and other cell cycle regulators. Herein, the recent findings on the regulation of the cell cycle by microRNAs are summarized, and the potential implications of miRNAs in anti-cancer therapies are discussed.     

Murine microRNAs implicated in liver functions and aging process

Small non-coding microRNAs (miRNAs) are involved in gene regulation in various cellular and developmental processes, including mechanisms of aging. Here, the mouse liver was used as a paradigm for the study of miRNAs implicated in the aging process in mammals. Expression profiling of 367 murine miRNAs (Sanger Version 8.2) was assessed in livers from 4 to 33 months old mice, and their predicted targets were compared with proteomic profiling data generated from the same animals. Gradual increases in the levels of miR-669c and miR-709 were observed from mid-age of 18-33 months, while miR-93 and miR-214 were significantly up-regulated only in extremely old liver. In contrast, we did not identify any miRNAs showing significant down-regulation with age. Interestingly, the up-regulated miRNAs' targets are associated with detoxification activity and regeneration capacity functions known to decline in old liver. In particular, three up-regulated miRNAs may contribute to the aging-related decline in oxidative defense by targeting various classes of glutathione S-transferases. Other proteins in decline in old liver and targeted by the up-regulated miRNAs are involved in mitochondrial functions or maintenance. Taken together, we identified the up-regulation of key miRNAs that may participate in the decline of regeneration and oxidative defense mechanisms in aging liver.