微RNA与肺癌

微RNA（miRNA）是一类约22nt的小分子非编码RNA,在转录后水平调控蛋白质的表达。大部分微RNA在基因组上定位于与肿瘤相关的脆性位点上,与肿瘤的发生、发展关系密切。在肺癌组织中,某些微RNA表达水平升高,而某些表达下降,它们充当＂癌基因＂或者＂抑癌基因＂的角色,可能在肺癌的诊断、治疗及预后监测中发挥重要作用。     

MicroRNAs与肿瘤

microRNA(miRNA)是一类对基因具有调控功能的内源性非编码小分子RNA,通过与靶mRNA完全或不完全互补配对,引起mRNA降解或翻译抑制,从而对基因转录后水平进行调控.目前认为miRNA在多种生物学过程中起着至关重要的作用,包括细胞增殖、分化、凋亡等.研究显示miRNA的表达异常能导致疾病甚至肿瘤的发生,有类似于抑癌基因或癌基因的功能.本文就miRNA在肿瘤发生和诊断方面的研究进展作一综述.     

miRNA在肝细胞癌中的研究进展和展望

微小RNA(microRNA, miRNA)是一类长度为二十几个核苷酸的内源性非编码调控RNA,通过序列特异性翻译抑制或mRNA裂解来调控基因表达,参与细胞发育、增殖、分化、凋亡等一系列重要生物学进程。近期的研究发现,miRNA具有癌基因和抑癌基因的作用,在肿瘤的发生和发展中起着重要的作用。已发现若干miRNA直接参与肝细胞癌的发生和发展,miRNA表达谱与肝细胞癌的诊断、分期、进展和预后等相关。作为一类新的分子靶标,miRNA应用于肝细胞癌的诊断和生物治疗具有广阔的前景。     

miR-20b-5p在肿瘤及其他疾病中的生物学功能

miRNAs是一类非编码的小RNA分子,在多种疾病的发病和治疗中发挥重要作用,可调控细胞增殖、细胞周期、凋亡和迁移等过程中关键基因的表达。miR-20b-5p属于miR-17家族,在多种肿瘤中和非肿瘤性疾病中存在异常表达。在肿瘤中,miR-20b-5p扮演着癌基因或抑癌基因的角色,可通过调控相应靶分子的表达影响肿瘤细胞的增殖、凋亡、侵袭与迁移等生物学行为,进而促进或抑制肿瘤的发生发展。该文对miR-20b-5p在肿瘤和非肿瘤性疾病中的生物学功能和机制进行简要综述。相信随着对miR-20b-5p的功能和机制的深入阐明,miR-20b-5p有望作为多种疾病的诊治靶点。     

PVT1在恶性肿瘤发生发展中的作用及机制

长链非编码RNA在调节细胞的生长、分化及其他生物学过程中具有重要作用,且与恶性肿瘤等常见疾病密切相关.人类长链非编码RNA PVT1的编码基因由于位于染色体8q24这一脆性位点且临近癌基因MYC而受到广泛关注.浆细胞瘤可变异位基因1(PVT1)在多种肿瘤中高表达,是潜在的癌基因;PVT1也能因染色体断裂重排而与其他基因形成新的融合基因影响恶性肿瘤的表型;PVT1还可与MYC基因相互作用,通过多种途径参与恶性肿瘤细胞的增殖、凋亡等调控.本文对PVT1在恶性肿瘤发生发展中的作用及其机制进行综述.     

miR-21在头颈肿瘤中的研究进展

微小RNA(micro RNA,miRNA)是一类小分子非编码RNA,可引起靶m RNA的降解或翻译抑制,从而对基因进行转录后表达调控,它在细胞生长、发育和衰老等生命过程中扮演着重要角色。miR-21在人类组织和细胞中较早发现,是广泛存在的miRNA之一,也是实体肿瘤中最常见的过高表达miRNA之一,在肿瘤的发生发展中可能发挥癌基因的作用。该文就miR-21在头颈肿瘤中的研究作一综述。     

miR-206在肺癌中的作用及机制研究进展

肺癌是现今全世界死亡率和发病率最高的恶性肿瘤,严重危及人类健康,其中超过85%的患者为非小细胞肺癌,5年预计生存期不超过16%。微小RNA(microRNA,mi RNA)是一类在基因组转录出来后直接在RNA水平上行使生物学功能的非编码RNA,大小约20～25个核苷酸组成,广泛存在于真核生物中。mi RNA可通过对癌基因或抑癌基因进行转录后调控而发挥类似于癌基因或抑癌基因的作用。MicroRNA-206(mi R-206)定位于人类第6号染色体上,最早从骨骼肌中发现,它参与人体中一系列的生物学过程例如细胞增殖,组织器官的生长及肿瘤的发生等。最近大量研究显示mi R-206在肿瘤细胞中表达失调,在肿瘤的生长、增殖、凋亡及侵袭、转移、耐药中发挥重要作用。本文就mi R-206在肺癌中的作用及其机制的研究进展作一综述。     

REV感染DF-1细胞分泌外体的生物信息学分析

该研究探讨了REV感染DF-1细胞分泌外体携带表达差异的蛋白质和微RNA(micro RNA,mi RNA),及其基因功能和参与的信号通路,为病毒致病机制研究提供了基础。通过蛋白组学和转录组学检测技术,筛选病毒感染组与对照组DF-1细胞分泌外体的差异蛋白质和mi RNA,并利用在线软件数据库对其进行GO功能富集和KEGG信号通路分析。结果筛选到101个差异表达蛋白质,其中56个表达上调,45个表达下调,共参与155条信号通路,参与蛋白质最多的是肿瘤相关通路;并筛选到3个表达上调的mi RNA,其中mi RNA-155、mi RNA-146a-3p编码的靶蛋白(整合蛋白)与差异蛋白质肌动蛋白相关2/3复合体(actinrelated 2/3 complexs,Arp2/3)共同参与肌动蛋白细胞骨架信号通路;差异蛋白质及mi RNA编码靶基因均含有病毒成分,并参与细胞信号转导、免疫、黏附、运动、生物调节等过程。该研究结果表明,REV感染DF-1细胞来源外体表达差异的蛋白质和mi RNA及其参与的生物学过程和信号通路与肿瘤形成密切相关,外体途径可能在REV致瘤机制中具有重要作用。     

EZH2在心脏与血管发育中的作用

Zeste基因增强子人类同源物2(enhancer of zeste homolog 2, EZH2)是多梳蛋白抑制复合物2(polycomb repressive complex 2, PRC2)的主要元件之一，利用组蛋白甲基化酶活性发挥经典作用，抑制靶基因的表达。此外，EZH2通过甲基化其他蛋白，作为蛋白支架分子募集转录相关分子介导转录激活，与lncRNA及miRNA相互作用等非经典途径调控各项生命活动，与干细胞分化和组织器官发育关系密切。EZH2及其功能相关分子在心脏发育、血管发生等过程中发挥着至关重要的作用。靶向敲除小鼠心脏Ezh2基因会影响心肌组织及内皮源性组织的正常发育，造成广泛性的心脏发育缺陷。EZH2参与调控正常组织和肿瘤组织的血管生成，维持新生血管完整性，并参与调控内皮间质化和内皮造血转化。本文探讨了EZH2在心脏和血管发生领域的影响效应、调控机制，及其与相关疾病的关系。     

MicroRNA与肿瘤相关的信号转导通路

信号转导通路在细胞代谢、生长、增殖、应激、发育和凋亡等生命活动中具有极为重要的作用。干扰这些通路将可能影响细胞的正常发育, 甚至导致肿瘤。MicroRNA(miRNA)是近年来在真核生物中发现的、在转录后水平负调节基因表达的一类长度约22个核苷酸的非编码小RNA, 其靶基因数目众多, 生物学功能广泛。在多种肿瘤中发现了miRNA的异常表达, 提示后者与肿瘤发生有关, 可能机制为调控癌基因或肿瘤抑制基因的表达。此外亦发现miRNA的靶基因有许多作用于肿瘤相关的信号转导通路。miRNA在肿瘤发生过程中的重要调控功能预示其将成为人类癌症诊断和治疗方面的新星。     

Human cytomegalovirus infection alters the expression of cellular microRNA species that affect its replication

The human genome encodes over 500 microRNAs (miRNAs), small RNAs (19 to 26 nucleotides [nt]) that regulate the expressions of diverse cellular genes. Many cellular processes are altered through a variety of mechanisms by human cytomegalovirus (HCMV) infection. We asked whether HCMV infection leads to changes in the expression of cellular miRNAs and whether HCMV-regulated miRNAs are important for HCMV replication. Levels of most miRNAs did not change markedly during infection, but some were positively or negatively regulated. Patterns of miRNA expression were linked to the time course of infection. Some similarly reregulated miRNAs share identical or similar seed sequences, suggesting coordinated regulation of miRNA species that have shared targets. miRNAs miR-100 and miR-101 were chosen for further analyses based on their reproducible changes in expression after infection and on the basis of having predicted targets in the 3' untranslated regions (3'-UTR) of genes encoding components of the mammalian target of rapamycin (mTOR) pathway, which is important during HCMV infection. Reporter genes that contain the 3'-UTR of mTOR (predicted targets for miR-100 and miR-101) or raptor (a component of the mTOR pathway; predicted site for miR-100) were constructed. Mimics of miR-100 and miR-101 inhibited expression from the mTOR construct, while only miR-100 inhibited the raptor construct. Together, miR-100 and miR-101 reduced mTOR protein levels. While the miR-100 and miR-101 mimics individually modestly inhibited production of infectious progeny, much greater inhibition was achieved with a combination of both (33-fold). Our key finding is that HCMV selectively manipulates the expression of some cellular miRNAs to help its own replication.     

MiR-101 and miR-144 Regulate the Expression of the CFTR Chloride Channel in the Lung

The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that plays a critical role in the lung by maintaining fluid homeostasis. Absence or malfunction of CFTR leads to Cystic Fibrosis, a disease characterized by chronic infection and inflammation. We recently reported that air pollutants such as cigarette smoke and cadmium negatively regulate the expression of CFTR by affecting several steps in the biogenesis of CFTR protein. MicroRNAs (miRNAs) have recently received a great deal of attention as both biomarkers and therapeutics due to their ability to regulate multiple genes. Here, we show that cigarette smoke and cadmium up-regulate the expression of two miRNAs (miR-101 and miR-144) that are predicted to target CFTR in human bronchial epithelial cells. When premature miR-101 and miR-144 were transfected in human airway epithelial cells, they directly targeted the CFTR 3′UTR and suppressed the expression of the CFTR protein. Since miR-101 was highly up-regulated by cigarette smoke in vitro, we investigated whether such increase also occurred in vivo. Mice exposed to cigarette smoke for 4 weeks demonstrated an up-regulation of miR-101 and suppression of CFTR protein in their lungs. Finally, we show that miR-101 is highly expressed in lung samples from patients with severe chronic obstructive pulmonary disease (COPD) when compared to control patients. Taken together, these results suggest that chronic cigarette smoking up-regulates miR-101 and that this miRNA could contribute to suppression of CFTR in the lungs of COPD patients.     

Identification of a common lupus disease-associated microRNA expression pattern in three different murine models of lupus

Background

Recent reports have shown that microRNAs (miRNAs) regulate vital immunological processes and have emerged as key regulators of immune system development and function. Therefore, it is important to determine miRNA dysregulation and its pathogenic contribution in autoimmune diseases, an aspect not adequately addressed thus far.

Methodology/Principal Findings

In this study, we profiled miRNA expressions in splenic lymphocytes from three murine lupus models (MRL-lpr, B6-lpr and NZB/W_F1) with different genetic background by miRNA microarray assays and Real-time RT-PCR. Despite the genetic differences among these three lupus stains, a common set of dysregulated miRNAs (miR-182-96-183 cluster, miR-31, and miR-155) was identified in splenocytes when compared with age-matched control mice. The association of these miRNAs with the disease was highlighted by our observation that this miRNA expression pattern was evident in NZB/W mice only at an age when lupus disease is manifested. Further, we have shown that the miRNA dysregulation in MRL-lpr mice was not simply due to the activation of splenocytes. By Real-time RT-PCR, we confirmed that these miRNAs were upregulated in both purified splenic B and T cells from MRL-lpr mice. miR-127 and miR-379, which were greatly upregulated in splenocytes from lpr mice, were moderately increased in diseased NZB/W mice. In addition, Real-time RT-PCR revealed that miR-146a, miR-101a, and miR-17-92 were also markedly upregulated in splenic T, but not B cells from MRL-lpr mice.

Conclusions/Significance

The identification of common lupus disease-associated miRNAs now forms the basis for the further investigation of the pathogenic contribution of these miRNAs in autoimmune lupus, which will advance our knowledge of the role of miRNAs in autoimmunity. Given that miRNAs are conserved, with regard to both evolution and function, our observation of a common lupus disease-associated miRNA expression pattern in murine lupus models is likely to have significant pathogenic, diagnostic, and/or therapeutic implications in human lupus.     

miRNAs调控lincRNAs的生物信息学预测与功能分析

基因间长链非编码RNAs(Long intergenic non-coding RNAs, lincRNAs)是位于蛋白编码基因之间的长度超过200 nt的非编码RNAs, 在动物中参与细胞周期调控、免疫监视、胚胎干细胞分化等多种生物学过程, 但是lincRNAs在大多数植物中的功能尚不清楚。MicroRNAs(miRNAs)是真核生物中一类在转录水平和转录后水平介导基因沉默的21 nt左右的内源性单链小非编码RNAs分子, 通过序列互补的方式调控靶标基因的表达。目前miRNAs的靶标研究主要集中于编码蛋白的基因, 而对于靶标为非编码RNAs的研究较少, 尤其在植物中的研究更为少见。为了系统挖掘植物中lincRNAs的功能, 文章整合miRNAs数据、cDNAs数据和降解组数据, 利用生物信息学方法找到拟南芥(Arabidopsis thaliana)337个成熟miRNAs在2708个lincRNAs上的可能结合位点, 构建了miRNAs-mRNAs-lincRNAs调控网络, 并根据竞争性内源(ceRNA)假说预测lincRNAs的功能, 为进一步阐明植物中miRNAs对lincRNAs的调控机制以及lincRNAs的功能奠定了基础。     

微小RNAs在肝癌中的作用机制及相关应用研究进展

微小RNAs(miRNAs)是一类内源性小型非编码RNA,可通过调控靶基因表达参与大多数生物学过程。近年来,miRNAs在肝癌发生发展进程中相关作用机制的研究逐渐深入,miRNAs作为其中关键调控因子和主要参与者,已成为肝癌早期诊断、靶向治疗和预后评估中的一个关键靶标。本文着重强调miRNAs在肝癌发生发展、多重耐药性中的作用以及作为肝癌潜在治疗靶点的价值,并就miRNAs在肝癌中的功能、分子作用通路以及应用三方面的相关研究进展进行综述。