Investigation of microRNA expression signatures in HCC via microRNA Gene Chip and bioinformatics analysis

BackgroundDysregulation of miRNAs is closely involved with hepatocellular carcinoma (HCC) progression, oncogenesis and signalling pathways. The aim of this study was to investigate differences in expression of miRNAs in HCC tissue in comparison to healthy liver tissue, as well as to explore the key miRNA-targeted genes.MethodsGene Chip microarray analysis was used to analyse differentially expressed miRNAs (DEMs) in tissues, and qRT-PCR was performed to validate the top 9 downregulated miRNAs. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed for target genes using the DAVID database. A protein-protein interaction (PPI) network of the target genes was created by STRING and visualised using Cytoscape. Three online miRNA databases were utilised to aid in the prediction of genes targeted by the top 10 significantly altered DEMs.ResultsIn total, 153 upregulated and 206 downregulated miRNAs were identified in HCC tissue. The genes targeted by the top 10 increased and decreased miRNAs were 6 and 1060, respectively. Moreover, FOXO1 was projected to be regulated by all twenty miRNAs. A PPI network was constructed that consisted of 956 nodes and 1298 edges. Four significant modules, consisting of 66 hub genes, were detected from the PPI system via MCODE. Functional enrichment demonstrated that miRNAs have a vital function in cancer development and advancement.ConclusionIn summary, our study identified DEMs in HCC tissue, major target genes and possible molecular mechanisms that underlie HCC, providing novel insights for treatment approaches.     

The carotid plaque as paradigmatic case of site-specific acceleration of aging process: The microRNAs and the inflammaging contribution

Atherosclerosis is considered a chronic inflammatory disease of arteries associated with the aging process. Many risk factors have been identified and they are mainly related to life-styles, gene-environment interactions and socioeconomic status. Carotid and coronary artery diseases are the two major atherosclerotic conditions, being the primary cause of stroke and heart attack, respectively. Nevertheless, carotid plaque assumes particular aspects not only for the specific molecular mechanisms, but also for the types of atheroma which may be associated with a better or a worst prognosis. The identification of circulating blood biomarkers able to distinguish carotid plaque types (stable or vulnerable) is a crucial step for the improvement of adequate therapeutic approaches avoiding or delaying endarterectomy in the oldest old individuals (> 80 years), a population predicted to growth in the next years. The review highlights the most recent knowledge on carotid plaque molecular mechanisms, focusing on microRNAs (miRs), as a site-specific accelerated aging within the conceptual framework of Geroscience for new affordable therapies.     

microRNAs：小分子在肿瘤中的重要作用

microRNAs是一类新型保守的微小非编码单链RNA,成熟的microRNAs通过与靶基因mRNA碱基形成不完全配对,引起mRNA降解及转录抑制。研究表明,microRNAs对细胞增殖、细胞分化和细胞凋亡具有重要的调控作用,microRNAs的表达异常与肿瘤的发生发展密切相关,肿瘤中既存在肿瘤抑制作用的microRNAs,也存在肿瘤促进作用的microRNAs。因此,microRNAs分子虽小,却在肿瘤发生、发展的过程中作用重大。     

microRNA与肿瘤

microRNA(miRNA)是近年来发现的一类长度约22个核苷酸非编码小分子RNA,它通过促使靶mRNA降解或抑制其翻译来调节靶基因的表达,在细胞的分化、增殖和凋亡,个体发育、机体代谢以及病毒感染中都具有重要的作用。随着研究的不断深入,目前认为miRNA在肿瘤发生发展过程中,具有与癌基因或抑癌基因相似的作用,有些致瘤病毒也编码miRNA影响宿主细胞,在肿瘤发生中可能具有重要的作用。利用这种作用,可将其作为抗肿瘤药物或者其他抗肿瘤药物的靶分子。     

力学刺激通过microRNA调控骨重建的研究进展

骨骼结构完整性和骨量的维持需要一定的力学刺激。研究表明,力学刺激可通过调控多种调节因子(例如激素、转录因子和信号分子等)参与骨重建过程。力学刺激可以通过调控微小RNA(microRNA,miRNA)表达在骨重建过程中起着至关重要的作用。然而,受力学刺激调控的miRNA在骨重建过程中的作用和机制尚不完全清楚。本文综述受力学刺激调控的miRNA在骨重建过程中的作用及其机制,并强调其在治疗骨质疏松中的潜在应用。     

miR‐155 is involved in tumor progression of mycosis fungoides

Biopsy specimens from 23 early stage and 19 tumor‐stage mycosis fungoides (MF) patients were evaluated for miR‐155 expression by real‐time qualitative PCR and compared with 15 biopsy specimens from patients with T‐cell‐rich inflammatory skin diseases. Significant upregulation of miR‐155 was found in MF tumors compared with both early‐stage MF lesions and controls. There was no difference in miR‐155 expression between early‐stage and inflammatory dermatoses. Using laser capture microdissection, it was found that miR‐155 was significantly higher in the lymphoma cells in tumor stage compared with the intraepidermal lymphocytes in early stage. In contrast, there was no difference in miR‐155 expression between the intraepidermal lymphocytes and the dermal lymphocytes in early‐stage MF. These findings suggest that although miR‐155 expression cannot serve to discriminate early‐stage MF from inflammatory dermatoses; however, it is involved in the switch from the indolent early stage into the aggressive tumor stage of the disease.     

微小RNA在膀胱肿瘤组织的表达及其临床意义

目的研究微小RNA（MicroRNAs/miRNAs）microRNAs在人类膀胱肿瘤组织中的表达及其作用。方法取安徽医科大学附属省立医院2009年手术切除的45例膀胱肿瘤组织标本及其肿瘤旁正常组织标本。通过microRNAs微阵点杂交法检测肿瘤组织及其癌旁正常组织的手术标本中microRNAs的表达情况,分析癌组织及其癌旁正常膀胱组织进行定性判断（癌和非癌）。结果人类膀胱肿瘤组织与正常膀胱组织相比,miR-223、miR-26b、miR-221、miR-103-1、miR-185、miR-23b、miR-203、miR-17-5p、miR-23a和miR-205表达显著上调（P〈0.005）。结论 miRNAs与膀胱肿瘤的发生发展有密切的联系,有可能成为一个有效的肿瘤标志物以进行膀胱肿瘤的早期预测和诊断。     

Novel epigenetic-based therapies useful in cardiovascular medicine

Epigenetic modifications include DNA methylation, his-tone modifications, and micro RNA. Gene alterations have been found to be associated with cardiovascular diseases, and epigenetic mechanisms are continuously being studied to find new useful strategies for the clinical management of afflicted patients. Numerous cardiovascular disorders are characterized by the abnormal methylation of Cp G islands and so specific drugs that could inhibit DNA methyltransferase directly or by reducing its gene expression(e.g., hydralazine and procainamide) are currently under investigation. The anti-proliferative and anti-inflammatory properties of histone deacetylase inhibitors and their cardio-protective effects have been confirmed in preclinical studies. Furthermore, the regulation of the expression of micro RNA targets through pharmacological tools is still under development. Indeed, large controlled trials are required to establish whether current possible candidate antisense micro RNAs could offer better therapeutic benefits in clinical practice. Here, we updated therapeutic properties, side effects, and feasibility of eme-rging epigenetic-based strategies in cardiovascular diseases by highlighting specific problematic issues that still affect the development of large scale novel therapeutic protocols.     

大鼠心肌肥厚过程中microRNAs的表达变化

目的:分析大鼠心肌肥厚过程中microRNAs(miRNAs)的表达变化。方法:通过肾上腹主动脉缩窄(abdominal aorticconstriction,AAC)的方法建立大鼠心肌肥厚模型。实时定量PCR检测大鼠肥厚心肌中miRNAs的表达变化。结果:大鼠AAC后1周,心重/体重比以及心肌肥厚标志分子心房钠尿肽、β-重链肌球蛋白的编码基因Nppa、myh7表达明显升高,表明心肌肥厚模型建立成功;对肥厚心肌的miRNAs表达检测表明,miR-199a表达显著升高,miR-1、miR-133、miR-181a及miR-499表达显著降低。AAC后4周,miR-21、miR-24和miR-214表达显著升高,miR-181a表达显著降低,miR-23a、miR-133、miR-145、miR-199a和miR-499表达无明显改变。结论:心肌肥厚后miRNAs表达发生改变,可能在心肌肥厚病理过程中发挥着重要的调节作用。