Regulation of tumor angiogenesis by microRNAs: State of the art

MicroRNAs (miRNAs, miRs) are small (21–25 nucleotides) endogenous and noncoding RNAs involved in many cellular processes such as apoptosis, development, proliferation, and differentiation via binding to the 3′-untranslated region of the target mRNA and inhibiting its translation. Angiogenesis is a hallmark of cancer, which provides oxygen and nutrition for tumor growth while removing deposits and wastes from the tumor microenvironment. There are many angiogenesis stimulators, among which vascular endothelial growth factor (VEGF) is the most well known. VEGF has three tyrosine kinase receptors, which, following VEGF binding, initiate proliferation, invasion, migration, and angiogenesis of endothelial cells in the tumor environment. One of the tumor microenvironment conditions that induce angiogenesis through increasing VEGF and its receptors expression is hypoxia. Several miRNAs have been identified that affect different targets in the tumor angiogenesis pathway. Most of these miRNAs affect VEGF and its tyrosine kinase receptors expression downstream of the hypoxia-inducible Factor 1 (HIF-1). This review focuses on tumor angiogenesis regulation by miRNAs and the mechanism underlying this regulation.     

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。     

MicroRNAs对动物皮肤和毛发发育调控作用的研究进展

MicroRNAs是近年来发现的一类由19-25个核苷酸组成的非编码单链小RNA分子,它们通过与靶基因mRNA3’UTR结合抑制靶基因的翻译,在转录后水平调控基因表达.MicroRNAs参与了包括细胞分化、增殖和凋亡及免疫系统应答在内的一系列发育调控和生物学过程.最近研究发现MicroRNAs在多种哺乳动物皮肤中均表达,并参与了哺乳动物皮肤及毛发发育的调控过程,这些都为研究这个新颖的调控因子在干细胞生物学和发育生物学中的功能奠定了基础.本文综述了近年来MicroRNAs对哺乳动物皮肤和毛发发育调控作用的研究状况.     

microRNA在非酒精性脂肪性肝病中的作用

microRNA(miRNA)是一类长度约为22个核苷酸的内源性非编码小分子RNA,通过影响靶mRNA的稳定性或抑制其翻译,从而对基因进行转录后水平的调控。研究发现,一些miRNA在非酒精性脂肪性肝病患者中出现差异性表达,这些差异性表达有多种功能,包括调节脂质和糖代谢,参与折叠蛋白反应、内质网应激、氧化应激、细胞分化、炎性反应及细胞凋亡。此文就miRNA在非酒精性脂肪性肝病病程中的潜在重要作用进行概述。     

MicroRNAs in skeletal and cardiac muscle development

MicroRNAs (miRNAs) are a recently discovered class of small non-coding RNAs, which are approximately 22 nucleotides in length. miRNAs negatively regulate gene expression by translational repression and target mRNA degradation. It has become clear that miRNAs are involved in many biological processes, including development, differentiation, proliferation, and apoptosis. Interestingly, many miRNAs are expressed in a tissue-specific manner and several miRNAs are specifically expressed in cardiac and skeletal muscles. In this review, we focus on those miRNAs that have been shown to be involved in muscle development. Compelling evidences have demonstrated that muscle miRNAs play an important role in the regulation of muscle proliferation and differentiation processes. However, it appears that miRNAs are not essential for early myogenesis and muscle specification. Importantly, dysregulation of miRNAs has been linked to muscle-related diseases, such as cardiac hypertrophy. A mutation resulting in a gain-of-function miRNA target site in the myostatin gene leads to down regulation of the targeted protein in Texel sheep. miRNAs therefore are a new class of regulators of muscle biology and they might become novel therapeutic targets in muscle-related human diseases.     

microRNA在肌肉发育中的功能研究进展

microRNA(miRNA)是一类非编码的小RNA分子,它通过对靶mRNA的翻译抑制和降解对基因表达起负调节作用。现在人们已经清楚地知道miRNA参与了增殖、分化、凋亡、发育等许多生物过程。一些miRNA在肌肉中特异表达,参与肌肉发育。该文重点介绍了参与肌肉发育的miRNA。已有证据表明肌肉miRNA在肌肉的增殖和分化过程中起了重要的调节作用,miRNA的调节异常和肌肉疾病有关。因此,miRNA是一类新的肌肉调控因子,它有可能成为畜禽肉产量提高和肌肉相关疾病治疗的新型靶标。     

The roles of microRNA in cancer and apoptosis

microRNAs (miRNAs) are highly conserved, non-protein-coding RNAs that function to regulate gene expression. In mammals this regulation is primarily carried out by repression of translation. miRNAs play important roles in homeostatic processes such as development, cell proliferation and cell death. Recently the dysregulation of miRNAs has been linked to cancer initiation and progression, indicating that miRNAs may play roles as tumour suppressor genes or oncogenes. The role of miRNAs in apoptosis is not fully understood, however, evidence is mounting that miRNAs are important in this process. The dysregulation of miRNAs involved in apoptosis may provide a mechanism for cancer development and resistance to cancer therapy. This review examines the biosynthesis of miRNA, the mechanisms of miRNA target regulation and the involvement of miRNAs in the initiation and progression of human cancer. It will include miRNAs involved in apoptosis, specifically those miRNAs involved in the regulation of apoptotic pathways and tumour suppressor/oncogene networks. It will also consider emerging evidence supporting a role for miRNAs in modulating sensitivity to anti-cancer therapy.     

Two new miR‐16 targets: caprin‐1 and HMGA1, proteins implicated in cell proliferation

Background information. miRNAs (microRNAs) are a class of non‐coding RNAs that inhibit gene expression by binding to recognition elements, mainly in the 3′ UTR (untranslated region) of mRNA. A single miRNA can target several hundred mRNAs, leading to a complex metabolic network. miR‐16 (miRNA‐16), located on chromosome 13q14, is involved in cell proliferation and apoptosis regulation; it may interfere with either oncogenic or tumour suppressor pathways, and is implicated in leukaemogenesis. These data prompted us to search for and validate novel targets of miR‐16. Results. In the present study, by using a combined bioinformatics and molecular approach, we identified two novel putative targets of miR‐16, caprin‐1 (cytoplasmic activation/proliferation‐associated protein‐1) and HMGA1 (high‐mobility group A1), and we also studied cyclin E which had been previously recognized as an miR‐16 target by bioinformatics database. Using luciferase activity assays, we demonstrated that miR‐16 interacts with the 3′ UTR of the three target mRNAs. We showed that miR‐16, in MCF‐7 and HeLa cell lines, down‐regulates the expression of caprin‐1, HMGA1a, HMGA1b and cyclin E at the protein level, and of cyclin E, HMGA1a and HMGA1b at the mRNA levels. Conclusions. Taken together, our data demonstrated that miR‐16 can negatively regulate two new targets, HMGA1 and caprin‐1, which are involved in cell proliferation. In addition, we also showed that the inhibition of cyclin E expression was due, at least in part, to a decrease in its mRNA stability.     

microRNA分子表达与调控研究的最新进展

microRNA(miRNA)是一类分子长度为19~24nt的微小RNA,通常在转录后水平调控靶基因的降解或抑制翻译。miRNA分子在进化上高度保守,已经发现越来越多的miRNA分子参与真核生物的生长发育、生理活性、细胞增殖、组织分化、细胞凋亡、复杂疾病调控等功能。通过介绍miRNA的起源、合成、修饰、细胞表达特点,以及对真核细胞调控等的最新进展与研究方法,阐述miRNA在基因表达调节中的重要地位及应用前景。     

The latest progress on miR‐374 and its functional implications in physiological and pathological processes

Non‐coding RNAs (ncRNAs) have been emerging players in cell development, differentiation, proliferation and apoptosis. Based on their differences in length and structure, they are subdivided into several categories including long non‐coding RNAs (lncRNAs >200nt), stable non‐coding RNAs (60‐300nt), microRNAs (miRs or miRNAs, 18‐24nt), circular RNAs, piwi‐interacting RNAs (26‐31nt) and small interfering RNAs (about 21nt). Therein, miRNAs not only directly regulate gene expression through pairing of nucleotide bases between the miRNA sequence and a specific mRNA that leads to the translational repression or degradation of the target mRNA, but also indirectly affect the function of downstream genes through interactions with lncRNAs and circRNAs. The latest studies have highlighted their importance in physiological and pathological processes. MiR‐374 family member are located at the X‐chromosome inactivation center. In recent years, numerous researches have uncovered that miR‐374 family members play an indispensable regulatory role, such as in reproductive disorders, cell growth and differentiation, calcium handling in the kidney, various cancers and epilepsy. In this review, we mainly focus on the role of miR‐374 family members in multiple physiological and pathological processes. More specifically, we also summarize their promising potential as novel prognostic biomarkers and therapeutic targets from bench to bedside.     

动物microRNA-181的功能与应用前景

microRNA(miRNA)是一类短的、进化上高度保守的非蛋白编码RNA, 长度一般为17~25个核苷酸, 通过阻止靶mRNA的翻译或与之互补配对诱导靶基因降解来调控其表达。文章简要总结了microRNA-181(miR-181)在动物细胞增殖、凋亡和分化中的作用和调控机制, 探讨了miR-181对淋巴细胞的增生分化、自身免疫、炎症和抗病毒等方面的免疫调控作用, 并简要分析了miR-181在肿瘤发生发展、诊断、治疗和预后等方面的功能与价值, 最后对miR-181的应用前景进行了探讨。研究miR-181家族成员的功能对于理解生命活动机制、疾病发生发展和找到诊治相关疾病的新方法等都具有重要的意义。     

microRNAs参与动脉粥样硬化疾病的发生

microRNAs (miRNAs)是一类非编码的小分子RNA（～22 nt）,可在转录后水平调控基因表达.miRNAs参与调控机体的多种生理和病理过程.近来研究表明,miRNAs可能与动脉粥样硬化疾病的发生和发展密切相关,在血管新生、炎症和脂蛋白代谢等方面发挥了关键作用.本文就miRNAs与动脉粥样硬化疾病相关的研究进展进行综述,为研究miRNAs在动脉粥样硬化的发病机制中的作用,以及为miRNAs能够作为诊断动脉粥样硬化疾病的生物标志物提供思路.     

miRNA靶基因的筛选方法及其相关网络资源

微小RNA（microRNA,miRNA）是一类广泛存在于动植物中,大小约22 nt的单链非编码小分子RNA.它通过与靶mRNA 3′末端非翻译区（untranslational region, UTR）结合,使mRNA降解或翻译抑制.大量的研究结果表明,miRNA在动植物的生长发育、细胞分化、细胞增殖与凋亡、肿瘤发生等诸多环节发挥着重要的调节作用.目前,miRNA靶基因的筛选方法主要有生物信息学筛选和实验方法两大类,且在互联网上拥有大量相关的网络共享资源.本文通过对现有miRNA靶基因的筛选方法及其相关网络资源进行整理与比较分析,以有效指导并辅助miRNA领域的研究.     

胰腺相关microRNAs研究进展

miRNAs是一类长约21-25nt的内源性的小非编码RNA(small noncoding RNA),它在基因的转录后调控中发挥着重要的作用。miRNAs可以通过与靶基因的mRNA的3'端UTR区完全或部分互补,进而降解该目的mRNA或阻止其翻译成相关蛋白,下调靶基因表达,以此参与个体发育、细胞分化、细胞增殖以及疾病发生过程中的基因表达调控。本文简要介绍miRNAs在胰腺发育、β细胞功能以及胰腺相关疾病中的研究进展。     

MicroRNA:新的心血管疾病生物标志物

近年来MicroRNA(miRNA)一直是医学生物学研究的热点。它作为一类非编码的小RNA,参与基因的转录和表达调控,因此人体的众多生命活动和疾病的发生、发展都与miRNA的变化密不可分。miRNA的作用因细胞特异性和目标mRNA的不同而异,miRNA可以通过影响细胞的分裂、增殖、凋亡和再生等表型的变化,参与疾病的损伤与修复过程。特别是近期研究人员进行了基于miRNA的疾病诊治研究,结果预示了良好的应用前景。     

靶向调控血管生成素miRNA的筛选和验证

血管生成素是一个重要的促血管生成因子,在细胞增殖、迁移和凋亡等过程中均发挥重要作用,但其具体的分子机制尚待阐明.miRNA是一类长约22 nt的小RNA,在转录后水平调控基因的表达,广泛参与各种生物学过程.本文探索了可直接调控血管生成素表达的miRNA,希望为阐明血管生成素的作用机制提供线索.首先,我们利用数据库预测得到8个可能靶向结合血管生成素mRNA 3′端非编码区的miRNA;然后,用实验方法验证它们与血管生成素的靶向关系,发现miR-1208、miR-196b、miR-296、miR-409-3p、miR-570和miR-641这6个miRNA可以不同程度地抑制血管生成素的mRNA和蛋白质表达水平,但只有miR-196b、miR-296、miR-409-3p和miR-641可以直接结合血管生成素mRNA的3′端非编码区;进而,在血管内皮细胞中分别过表达这4个miRNA,发现miR-196b、miR-409-3p和miR-641可以抑制血管内皮细胞的细胞增殖,而miR-196b、miR-296和miR-409-3p可以抑制血管内皮细胞的管腔形成.以上结果表明,细胞内有多个miRNA调控血管生成素的表达,它们可能协调调节血管生成,抑或在血管生成的不同阶段发挥作用.我们的工作还为“一种mRNA可被多种microRNA调节,而一种microRNA可调节多种mRNA”假说提供了部分证据.