MicroRNA与肺癌发生、诊断及治疗

微小RNA(miRNAs)是一大类小的非编码RNA,它通过与靶mRNA 3′非翻译区部分互补配对来调节特定基因的表达。近来研究表明,miRNA可作为癌基因或抑癌基因在肺癌发生发展过程中起重要作用。比较癌组织和非癌组织中miRNA表达谱的差异可筛选出部分miRNA分子作为肺癌诊断和预后判断的潜在生物标记。调节具有致癌或抑癌功能的miRNA表达可能成为肺癌治疗新方法,而结合传统放化疗及其敏感性miRNA标志也为肺癌治疗研究提供了新的策略。该文对miRNA在肺癌发生与发展、基因诊断和治疗中的作用做一综述。     

microRNAs:心血管疾病重要的调控因子

微RNA（microRNA,miRNA）是一类内源性19—25个核苷酸大小的非编码RNA分子,在进化中具有高度保守性,并且能够通过碱基匹配原则识别靶基因3’非翻译区的靶位点,从而抑制编码蛋白靶基因的翻译或（和）降解靶基因。目前的研究表明,miRNA在生物体发育、心血管疾病以及肿瘤发生等过程中起重要作用。本文对miRNA在心血管系统生理病理中的作用做一综述。     

siRNA与miRNA在生物基因调控中的沉默机制比较

siRNA和miRNA的沉默机制是生物基因调控的重要手段之一. 小干扰RNA（small interfering RNA,siRNA）是RNA干扰的引发物,激发与之互补的目标mRNA沉默. 非编码RNA中的微小RNA（microRNA,miRNA）,能够识别特定的目标mRNA,通过与mRNAs的3′ 非翻译区结合,影响该目标蛋白的翻译水平. siRNA和miRNA的基因调控机制对生物学研究及疾病的病因和治疗等有直接影响. 本文主要对siRNAs和miRNAs的生物起源及沉默机制进行比较性论述：提出Dicers酶蛋白、Ago蛋白以及20 nt~25 nt的双链RNAs的 3类大分子是RNA沉默的特征结构,并进行了说明性论述|总结性叙述了siRNA和miRNA的2类小分子经典沉默机制,并提出其异同点. 最后,本文根据近期研究进展,对siRNA和miRNA的生物起源及沉默机制提出了新的疑问.     

微RNA与肺癌

微RNA(microRNA,miRNA)是一类长度为21～22nt的非编码RNA分子,其通过转录后基因沉默调控靶基因的活性,在包括肺癌在内的肿瘤发生中起重要作用。随着对miRNA靶基因及miRNA分子行为认识的提高,miRNA很有可能成为癌症治疗新的途径。本文介绍了miRNA的生成,miRNA在肺癌中的作用机理及诊断治疗方面的最新进展。     

MicroRNA研究进展

近年来,在许多真核生物中发现了一类能时序调控发育的、长度约为22个核苷酸（nt）的非编码小分子RNA,称为microRNA(miRNA)。它由RNaseⅢ蛋白Drosha和Dicer共同酶解作用产生,由Exportin-5转运出核,通过与small interfering RNA(siRNA)相似的机制,导致mRNA降解,或者与mRNA的3’端非翻译区结合,阻遏转录后翻译。miRNA在发育和某些人类疾病发生中有着重要作用。     

microRNA的功能及其临床应用

microRNA(miRNA)是一类长度为19~25个核苷酸的非常保守的非编码小RNA分子,在真核生物体内通过与m RNA的3'非翻译区序列不完全互补结合促使m RNA降解或抑制翻译,从而在转录后水平调控基因表达。miRNA在生物体内参与了细胞增殖与凋亡、生长发育、代谢活化、DNA修复等一系列生物学过程,与多种疾病尤其是肿瘤的发生发展密切相关。对miRNA的功能研究已发展到其分子机制层面,大量集中于其靶基因的预测和鉴定及调控相关表观遗传因子,为疾病的诊断、治疗及预后提供了新的线索。我们就miRNA的合成、功能研究及miRNA在临床上的应用前景做简要综述。     

微核糖核酸在相关疾病发生发展中的调节作用

微核糖核酸（miRNA）是一类长度为18～25个核苷酸的内源性非编码小RNA,在转录后基因调控中发挥功能。miRNA通过降解mRNA或抑制蛋白翻译的方式调节特异基因表达。miRNA在多种生物进程包括发育、代谢、增殖、分化和凋亡中起到关键作用。miRNA的表达变化与相应的多种人类疾病及其发生发展密切相关。阐明miRNA对疾病基因的调节作用及其分子机制,将为人类某些疾病的基因治疗提供新的思路。     

多发性骨髓瘤相关microRNA的研究进展

microRNA(miRNA)是一种内源性非编码的单链小分子RNA,长度约19~24个核苷酸,通过靶向结合mRNA的3′非翻译区域(3′UTR)区域,抑制翻译或者降解靶标mRNA而调节基因的表达.miRNA参与一些重要的生理、病理学过程,包括细胞增殖、分化、生长和凋亡等.大量研究发现,miRNA与多发性骨髓瘤(multiplemyeloma,MM)的发生、发展及诊断治疗等有着密切关系.深入探讨MM相关miRNA的调节机制和功能等,可为MM发病机制的研究及诊治提供新的思路.     

miRNA，siRNA，saRNA与基因表达调控

近年来的研究发现,生物体内存在着大量的非编码RNA（non．codingRNAs,ncRNA）,它们在染色质修饰、基因转录、RNA剪接和mRNA翻译等多种水平上参与了基因表达的调控。ncRNA中的小分子RNA如miRNA能够识别特定的目标mRNA,通过与mRNAs3’非翻译区结合,影响mRNA转录及蛋白质翻译;siRNA是RNA干扰的引发物,能够导致与dsRNA同源的mRNA降解,进而抑制相应基因表达;saRNA是目前最新发现的一种靶向目的基因启动子区的在转录水平激活目的基因表达的dsRNA。miRNA、siRNA和saRNA在生成机制、作用途径等方面关系密切,既区别又相互联系,小分子RNA的研究将是今后分子生物学的研究热点之一。     

MicroRNA对动脉粥样硬化发生的调控作用及其临床应用

MicroRNA（miRNA）是新发现的基因表达调控因子,由长约21～25个核苷酸的单 链RNA分子构成,是非编码小RNA. 它可以通过与特定mRNA的3′非翻译区（3′- untranslated region,3′UTR）相结合,抑制mRNA编码蛋白质的翻译过程来调控基因表达. 动脉粥样硬化(atherosclerosis, AS)是一种慢性炎症性疾病,是多种心血 管疾病的病理基础.最近,研究发现多个miRNA与动脉粥样硬化的发生发展有关, 且其在血液和体液中稳定存在并高度保守. 本文主要综述了miRNA对动脉粥样硬化进程的调节作用及以其为靶点的相关临床研究,旨在阐明miRNA成为动脉粥样硬化诊断与治疗新靶点的重要意义.     

循环miRNA 表达谱在肺癌早期诊断、判断预后和指导化疗中的应用

MicroRNA(miRNA)是一种高保守,长度大概21-23个核苷酸,非蛋白编码RNA,起着调节基因表达的作用。近年来有关miRNA与肺癌的关系已经得到证实,并且成为当前研究的热点。miRNA能整体调节基因表达,这使得miRNA表达谱在作为生物信号方面比蛋白编码基因更具有提示作用。最近发现miRNA以被保护的状态存在于循环血液中,这使得miRNA表达的发现具有非侵袭性、重现性以及易检测性。研究显示血浆miRNA表达谱可作为肺癌生物信号分子,在肺癌早期诊断、判断预后和指导化疗药物应用等方面具有重要作用。本文将对血浆miRNA与肺癌的研究进展,以及在肺癌早期诊断、判断预后和指导化疗药物应用等方面作一综述。     

外泌体源性miRNAs在肺癌发生发展中的作用

外泌体(exosomes)是细胞分泌的纳米级细胞外囊泡.外泌体通过释放其内的生物活性大分子,比如微小RNA(microRNA,miRNA)到受体细胞,从而介导细胞间交流通讯. MiRNAs作为一类主要在转录后水平负向调控靶mRNAs的非编码RNAs,其在外泌体中含量最为丰富.在肺癌中,miRNAs经肿瘤细胞分泌的外泌体转运释放而发挥重要的作用.本文主要讨论了外泌体源性miRNAs在肺癌发生发展的各个阶段,包括血管生成、细胞增殖、侵袭转移、免疫逃逸、耐药等方面的作用,以及其在作为新型肺癌诊断和预后标志物方面的临床价值.     

Role of exosomal microRNAs in lung cancer biology and clinical applications

Exosomes, small extracellular vesicles ranging from 30 to 150 nm, are secreted by various cell types, including tumour cells. Recently, microRNAs (miRNAs) were identified to be encapsulated and hence protected from degradation within exosomes. These exosomal miRNAs can be horizontally transferred to target cells, in which they subsequently modulate biological processes. Increasing evidence indicates that exosomal miRNAs play a critical role in modifying the microenvironment of lung cancers, possibly facilitating progression, invasion, angiogenesis, metastasis and drug resistance. In this review, we summarize the novel findings on exosomal miRNA functions during lung cancer initiation and progression. In addition, we highlight their potential role and challenges as biomarkers in lung cancer diagnosis, prognosis and drug resistance and as therapeutic agents.     

Cervical cancer development,chemoresistance, and therapy: a snapshot of involvement of microRNA

Cervical cancer (CC) is one of the leading causes of death in women due to cancer and a major concern in the developing world. Persistent human papilloma virus (HPV) infection is the major causative agent for CC. Besides HPV infection, genetic and epigenetic factors including microRNA (miRNA) also contribute to the malignant transformation. Earlier studies have revealed that miRNAs participate in cell proliferation, invasion and metastasis, angiogenesis, and chemoresistance processes by binding and inversely regulating the target oncogenes or tumor suppressor genes. Based on functions and mechanistic insights, miRNAs have been identified as cellular modulators that have an enormous role in diagnosis, prognosis, and cancer therapy. Signatures of miRNA could be used as diagnostic markers which are necessary for early diagnosis and management of CC. The therapeutic potential of miRNAs has been shown in CC; however, more comprehensive clinical trials are required for the clinical translation of miRNA-based diagnostics and therapeutics. Understanding the molecular mechanism of miRNAs and their target genes has been useful to develop miRNA-based therapeutic strategies for CC and overcome chemoresistance. In this review, we summarize the role of miRNAs in the development, progression, and metastasis of CC as well as chemoresistance. Further, we discuss the diagnostic and therapeutic potential of miRNAs to overcome chemoresistance and treatment of CC.

     

Molecular characterization of lung cancer: A two-miRNA prognostic signature based on cancer stem-like cells related genes

Lung cancer is one of the deadliest cancers worldwide. To increase the survival rate of lung cancer, it is necessary to explore specific prognosis markers. More and more evidence finds that noncoding RNA is closely associated with the survival of lung cancer, and cancer stem cells (CSCs) also play a significant role in the progress of lung cancer. The objective of this study is to find CSLCs genes that affect the prognosis of lung cancer. The differential expression of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs) in the Cancer Genome Atlas (TCGA) database and differential expression data from microarray of CD326⁺ and CD326⁻ A549 cell are intersected to identify stable and consistent expression genes (2 lncRNAs, 15 miRNAs, and 134 mRNAs). The intersection of lncRNAs and miRNAs is analyzed by univariate and multivariate Cox regression to obtained prognostic genes. Two miRNAs (miR-30b-5p and miR-29c-3p) are significantly correlated with the overall survival rate. Then using these two miRNAs to construct a risk score model as a prognosis signature of lung cancer. Subsequently, we analyzed the association between two miRNAs and clinical information of lung cancer patients, of which T stage, Neoplasm cancer and risk score (P < .05) can be used as independent prognostic indicators of lung cancer. Finally, target genes of 2 miRNAs and 134 mRNAs were annotated with Gene Ontology and analyzed with Kyoto Encyclopedia of Genes and Genomes pathway, and verified with the GEO database. In summary, this study illustrates the role of miRNAs in the promotion of lung cancer by CSCs, which is important to find molecular biomarkers of lung cancer.     

MicroRNAs in human diseases

The discovery of microRNAs (miRNAs), a new class of negative regulator that represses gene expression by pairing with their target messenger RNAs (mRNAs), has revealed a natural pathway for controlling gene expression. There are hundreds of miRNAs encoded in the human genome and thousands of target mRNAs, which illustrates the important regulatory roles of miRNAs in cell developmental, differentiation, proliferation and apoptosis pathways. In this scenario, it is not surprising that deregulated miRNAs have been involved in the pathogenesis of many human diseases. The recent development of technologies and compounds to identify and modulate miRNAs has opened new avenues for diagnosis, prognosis and therapeutic applications. Here, we summarize most of the recent patents related to the detection and profiling of miRNAs from pathological samples and to miRNA modulators used as new therapies for disease, including cancer and viral infections, as well as methods for their delivery.     

miRNA在防治非小细胞肺癌中的研究进展

微RNA(micro RNAs;mi RNA)是一类长度约为22核苷酸的非编码核苷酸,能在转录后水平抑制蛋白的翻译而调控靶向基因的表达。非小细胞肺癌(NSCLC)占所有肺癌比例的80%,确诊后一般为晚期,且具有早期确诊率低,治疗效果差,治疗后易复发,预后不良等特征。目前用于治疗NSCLC的方法主要是手术、放化疗、中医中药治疗以及生物免疫治疗,总体治疗效果不明显,死亡率高。近年来,大量研究表明mi RNA在癌症的发生发展、转移及复发中具有重要的作用,但目前尚未建立系统规范的使用mi RNA对NSCLC诊断、治疗、预后的标准化方案,临床实施难度大。本文就近几年来mi RNA在NSCLC诊断、治疗及预后功能上进行综述,期望有助于促进mi RNA在实际临床中发挥其应有的作用。