外周血miRNA作为肿瘤标志物的研究进展

miRNA是一类长度为20～24个核苷酸的非编码小分子RNA,与靶基因3'端非编码区不完全配对,从而抑制靶基因mRNA的翻译,影响个体发育、细胞凋亡、细胞增殖和分化等生命活动,与肿瘤的发生、转移和耐药等病理进程密切相关.近年来的研究发现,除了组织和细胞中的miRNA,外周血miRNA的表达也表现为显著的肿瘤相关性、组织特异性和表达稳定性,符合肿瘤标志物的要求.本文就外周血miRNA作为肿瘤标志物的研究进展进行综述.     

微小RNAs在乳腺癌中的应用价值

乳腺癌是目前女性最常见的恶性肿瘤,2012年全球共有170万乳腺癌新增病例,且乳腺癌的发病率和死亡率持续上升.肿瘤标志物在乳腺癌的早期诊断、个体化治疗、预后及疗效预测等方面发挥重要作用.目前常见的肿瘤标志物包括蛋白酶类、肿瘤特异性抗原、代谢产物等.然而,这些标志物特异性并不高,特别是在肿瘤早期筛查、良恶性肿瘤的区分和低度恶性肿瘤的诊断方面特异性较低.微小RNA（microRNA,miRNA）是一类调控基因表达的非编码小分子RNA,参与多种生物学信号通路的调节,组织或循环中miRNA的异常表达与乳腺癌密切相关.循环miRNA作为非侵袭性、实时监测的新型肿瘤标志物,在乳腺癌领域得到了广泛研究,可以作为分析肿瘤转移、预后判断、疗效评价和个体化治疗的有利依据.本文介绍miRNA与乳腺癌的相关性,并针对循环miRNA在乳腺癌的诊断、预后以及疗效评价方面的应用价值作一综述.     

环状RNA在肿瘤表观遗传学中的机遇及挑战

表观遗传修饰异常与肿瘤发生发展密切相关，其中非编码RNA是三种常见的表遗传修饰方式之一，而环状RNA（circular RNA，circRNA）作为一类具有闭合环状结构的非编码RNA分子，研究证实可作为miRNA的海绵起调控作用，参与肿瘤细胞增殖、分化、凋亡、侵袭、转移等多种病理生理调控。同时circRNA具有特异性表达、高度保守和高稳定性等特点，因此circRNA相关标志物可能成为肿瘤早期诊断、治疗以及预后评估的有效标志物，也为肿瘤诊疗提供了无创检测的新契机。本文主要阐述circRNA相关标志物在肿瘤中的研究进展及应用现状，并探讨其在肿瘤表观遗传学中的机遇和挑战。     

新型肿瘤分子标志物循环微小RNA的研究进展

肿瘤作为威胁人类健康的最主要疾病之一,早期诊断、个体化治疗方案的选择及复发的判断对于预后有重要意义.微小RNA（miRNA）是一类具有调节作用的小片段RNA分子,近几年逐渐成为研究热点.miRNA分子在体液及循环系统中稳定存在,而且某些miRNA在肿瘤患者中特异性表达,对肿瘤的诊断及预后具有指导意义.文章综述有关循环miRNA的研究报道,探讨循环miRNA作为新型肿瘤分子标志物的意义及其局限性.     

miRNA与非小细胞肺癌的研究进展

微小RNA（miRNA）是人类基因组中广泛存在的一类非编码单链小分子RNA,在转录后水平以完全或非完全互补的方式与其靶mRNA相结合,调节相应mRNA表达,影响生物学性状。研究发现miRNA的重要进程包括基因表达调控、细胞增殖分化等与肿瘤密切相关。目前miRNA在非小细胞肺癌的研究尚处于起步阶段,主要包括miRNA在非小细胞肺癌中的表达检测;miRNA与非小细胞肺癌的发生、预后的相关性及其机制的研究;以及miRNA在NSCLC的诊断、治疗及预后判断等方面的应用。     

微小RNA与肿瘤的关系

微小RNA（microRNA,miRNA）是一类长度约为22个核苷酸的内源性单链非编码小RNA分子,通过碱基配对原则与靶基因完全或不完全互补结合,调控基因表达,调节细胞分化、细胞增殖、血管生成和细胞凋亡等过程。miRNA异常表达,可作为癌基因或抑癌基因介导恶性肿瘤的发生发展、复发和转移等。miRNA的表达具有组织特异性,使其能够在不明组织来源肿瘤中起诊断作用。通过不同的药物输送途径上调或抑制miRNA的表达,靶向调节miRNA成为一种新的治疗手段,开启了肿瘤治疗新模式。     

肺癌诊治和预后判断分子标志物miRNA

肺癌是目前全世界发病率第一、死亡率最高的肿瘤。肺癌的早期诊断和有效治疗是提高患者生存率的关键。miRNA是一类内源性、高度保守的非编码小分子RNA,在肺癌的发生、发展中起着重要作用。近年来,肺癌诊断、治疗和预后判断分子标志物miRNA的研究进展迅速,本文就miRNA作为肺癌早期诊断、预后判断和疗效预测分子标志物的研究进展,以及目前存在的问题做一综述。      

诊断肿瘤新型标志物血清miRNA

 微小RNA(miRNA )功能失调与肿瘤的发生、发展密切相关。血清miRNA不仅具有良好的稳定性,而且有显著的肿瘤相关性和组织特异性。血清miRNA的检测具有获取简便、创伤小、技术快速等优点,因此可作为新的诊断肿瘤的分子标志物。     

循环microRNA在胃癌临床诊断及预后中的研究进展

microRNAs（miRNAs）是一类长约22个核苷酸的内源性非编码RNA分子,通过与靶基因mRNA 3'-非编码区相互作用引起靶基因mRNA降解或翻译抑制,在转录后水平发挥着重要的调控功能。有关miRNA在癌症中的功能已经进行了广泛研究,最近发现外周血等体液中存在miRNA,并且多种癌症患者的外周血miRNA表达谱发生特异性改变。越来越多证据表明循环miRNA可作为一种新颖的分子标志物应用于癌症诊断和预后评估。本文针对循环miRNA在胃癌诊断、评估和预后等方面的研究进展进行综述。     

微小RNA与肿瘤研究进展

微小RNA(microRNA,miRNA)是一种长度约为22 nt的非编码RNA,它们通过miRNA介导的特异性的基因沉默导致靶mRNA降解及抑制蛋白质的合成调控转录后基因表达水平.miRNA对细胞的增殖、分化和凋亡有重要的调节作用,在正常组织和肿瘤组织中的表达显著不同,参与了肿瘤的发生、发展和预后.该文主要讨论miRNA在肿瘤方面的研究进展.     

循环血液外泌体miRNA在卵巢癌发生发展中作用及其诊断价值的研究进展

卵巢癌（ovarian cancer,OC）是女性恶性肿瘤死亡的主要原因。由于卵巢癌无症状发展,缺乏早期诊断标志物,大多数患者在晚期才被诊断出来。早期检测卵巢癌可显著提高总生存率,在过去的几十年里,微小RNA（miRNA）在癌症的发展中起着重要的作用,因此引起了极大的关注。miRNA可以在循环血液中稳定存在(如包裹在外泌体中),并可通过外泌体的分泌和转移在肿瘤细胞之间和肿瘤细胞微环境的沟通中发挥重要的作用。此外,外泌体miRNA在卵巢癌中的表达是失调的,可能反映肿瘤的恶性特征。因此评估外泌体来源的循环miRNA可能会为卵巢癌提供一类新的非侵袭性生物标志物。本综述概述了有关外泌体miRNA在卵巢癌发生发展过程中的作用以及循环血液外泌体miRNA作为卵巢癌早期诊断潜在生物标志物的现状。     

MicroRNA expression profiling in prostate cancer

MicroRNAs (miRNA) are small, endogenously expressed noncoding RNAs that negatively regulate expression of protein-coding genes at the translational level. Accumulating evidence, such as aberrant expression of miRNAs, suggests that they are involved in the development of cancer. They have been identified in various tumor types, showing that different sets of miRNAs are usually deregulated in different cancers. To identify the miRNA signature specific for prostate cancer, miRNA expression profiling of 6 prostate cancer cell lines, 9 prostate cancer xenografts samples, 4 benign prostatic hyperplasia (BPH), and 9 prostate carcinoma samples was carried out by using an oligonucleotide array hybridization method. Differential expression of 51 individual miRNAs between benign tumors and carcinoma tumors was detected, 37 of them showing down-regulation and 14 up-regulation in carcinoma samples, thus identifying those miRNAs that could be significant in prostate cancer development and/or growth. There was a significant trend (P=0.029) between the expression of miRNAs and miRNA locus copy number determined by array comparative genomic hybridization, indicating that genetic aberrations may target miRNAs. Hierarchical clustering of the tumor samples by their miRNA expression accurately separated the carcinomas from the BPH samples and also further classified the carcinoma tumors according to their androgen dependence (hormone naive versus hormone refractory), indicating the potential of miRNAs as a novel diagnostic and prognostic tool for prostate cancer.     

Research on the Typical miRNA and Target Genes in Squamous Cell Carcinoma and Adenocarcinoma of Esophagus Cancer with DNA Microarray

To identify the typically expressed miRNAs in squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of esophagus cancer and their target genes, and explore the related functions and pathways, providing potential biomarkers for esophageal carcinoma diagnosis and treatment. Gene expression profile GSE13937 was downloaded from Gene Expression Omnibus database which includes 152 samples, paired non-cancerous and cancerous, 44 SCC cases and 32 ADC cases; the differentially expressed miRNAs were identified with limma packages in R language after the data were normalized. Selected differentially expressed miRNAs were further analyzed using bioinformatics methods. Firstly, verified targets of miRNAs in two miRNA databases: miRecods and miRTarBase were integrated to select the targets genes of differentially expressed miRNAs. Next, String software was used to construct the target genes interaction network. Finally, function and pathway enrichment analysis of genes in the interaction network was carried out with Gestalt software. Up-regulated hsa-miR-21 and down-regulated hsa-miR-203 were identified by comparing normal and cancer tissue samples, and the targets genes regulated by these two miRNAs were most significantly related to cell cycle function and pathway, especially in the phase of G1/S. The two differentially expressed miRNA: hsa-miR-21 and hsa-miR-203 provide evidence for early diagnosis and treatment of esophageal carcinoma. The functions and pathways of target genes shows that deep understanding of cell cycle G1/S will help to illustrate the relationship between cell cycle regulation and pathogenesis of esophageal cancer.     

新疆南部维吾尔族宫颈鳞癌microRNA研究

背景与目的：宫颈癌是新疆地区尤其是新疆南部维吾尔族高发肿瘤,发病机制尚不清楚。微小RNA(microRNA,miRNA)是一类具有重要调控作用的非编码小分子RNA,其表达及功能失调与肿瘤的发生、发展密切相关。本研究筛选并初步研究新疆南部维吾尔族宫颈鳞癌差异表达的miRNA,预测并分析靶基因功能。方法：采用miRNA微阵列芯片技术对5例人乳头瘤病毒(human papillomavirus,HPV)16阳性的新疆南部维吾尔族宫颈鳞癌进行miRNA筛选,应用实时定量RT-PCR方法对筛选出差异表达的miRNA进行初步验证,并检测及分析在83例宫颈癌中的表达结果,应用targetscan、miRwalk、miRanda及Pictar四种软件预测其靶基因。结果：新疆南部维吾尔族HPV16阳性宫颈鳞癌差异表达基因18个,对差异表达显著的miRNA-138和miRNA-720进行了初步验证并预测靶基因,预测两者共同的靶基因是EZH2;与40例正常对照相比,miRNA-138、miRNA-720在83例宫颈鳞癌组织中均表达下调(P<0.05);下调的miRNA-138、miRNA-720与淋巴结转移、脉管浸润有关(P<0.05),但与年龄、宫颈壁累及范围及HPV16感染无明显关系(P>0.05);miRNA-720与临床分期、肿瘤体积有关(P<0.05)。结论：miRNA-138、miRNA-720在新疆南部维吾尔族宫颈鳞癌组织中均表达下调,两者共同的靶基因是EZH2,可能与宫颈癌的侵润和转移有关。     

MicroRNA in colorectal cancer: from benchtop to bedside

Colon carcinogenesis represents a stepwise progression from benign polyps to invasive adenocarcinomas and distant metastasis. It is believed that these pathologic changes are contributed by aberrant activation or inactivation of protein-coding proto-oncogenes and tumor suppressor genes. However, recent discoveries in microRNA (miRNA) research have reshaped our understanding of the role of non-protein-coding genes in carcinogenesis. In this regard, a remarkable number of miRNAs exhibit differential expression in colon cancer tissues. These miRNAs alter cell proliferation, apoptosis and metastasis through their interactions with intracellular signaling networks. From a clinical perspective, polymorphisms within miRNA-binding sites are associated with the risk for colon cancer, whereas miRNAs isolated from feces or blood may serve as biomarkers for early diagnosis. Altered expression of miRNA or polymorphisms in miRNA-related genes have also been shown to correlate with patient survival or treatment outcome. With further insights into miRNA dysregulation in colon cancer and the advancement of RNA delivery technology, it is anticipated that novel miRNA-based therapeutics will emerge.     

Characterization of microRNA transcriptome in lung cancer by next-generation deep sequencing

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death. Systematically characterizing miRNAs in NSCLC will help develop biomarkers for its diagnosis and subclassification, and identify therapeutic targets for the treatment. We used next-generation deep sequencing to comprehensively characterize miRNA profiles in eight lung tumor tissues consisting of two major types of NSCLC, squamous cell carcinoma (SCC) and adenocarcinoma (AC). We used quantitative PCR (qPCR) to verify the findings in 40 pairs of stage I NSCLC tissues and the paired normal tissues, and 60 NSCLC tissues of different types and stages. We also investigated the function of identified miRNAs in lung tumorigenesis. Deep sequencing identified 896 known miRNAs and 14 novel miRNAs, of which, 24 miRNAs displayed dysregulation with fold change ≥4.5 in either stage I ACs or SCCs or both relative to normal tissues. qPCR validation showed that 14 of 24 miRNAs exhibited consistent changes with deep sequencing data. Seven miRNAs displayed distinctive expressions between SCC and AC, from which, a panel of four miRNAs (miRs-944, 205-3p, 135a-5p, and 577) was identified that cold differentiate SCC from AC with 93.3% sensitivity and 86.7% specificity. Manipulation of miR-944 expression in NSCLC cells affected cell growth, proliferation, and invasion by targeting a tumor suppressor, SOCS4. Evaluating miR-944 in 52 formalin-fixed paraffin-embedded SCC tissues revealed that miR-944 expression was associated with lymph node metastasis. This study presents the earliest use of deep sequencing for profiling miRNAs in lung tumor specimens. The identified miRNA signatures may provide biomarkers for early detection, subclassification, and predicting metastasis, and potential therapeutic targets of NSCLC.     

Large‐scale genome‐wide screening of circulating microRNAs in clear cell renal cell carcinoma reveals specific signatures in late‐stage disease

Circulating miRNAs have shown great promises as noninvasive diagnostic and predictive biomarkers in several solid tumors. While the miRNA profiles of renal tumors have been extensively explored, knowledge of their circulating counterparts is limited. Our study aimed to provide a large‐scale genome‐wide profiling of plasma circulating miRNA in clear‐cell renal cell carcinoma (ccRCC). Plasma samples from 94 ccRCC cases and 100 controls were screened for 754 circulating micro‐RNAs (miRNA) by TaqMan arrays. Analyses including known risk factors for renal cancer—namely, age, sex, hypertension, obesity, diabetes, tobacco smoking and alcohol consumption—highlighted that circulating miRNA profiles were tightly correlated with the stage of the disease. Advanced tumors, characterized as stage III and IV, were associated with specific miRNA signatures that significantly differ from both controls and earlier stage ccRCC cases. Molecular pathway enrichment analyses of their gene targets showed high similarities with alterations observed in renal tumors. Plasma circulating levels of miR‐150 were significantly associated with RCC‐specific survival and could marginally improve the predictive accuracy of clinical parameters in our series, including age at diagnosis, sex and conventional staging. In summary, our results suggest that circulating miRNAs may provide insights into renal cell carcinoma progression.     

食管鳞状细胞癌中miRNAs的研究进展

食管鳞状细胞癌（esophageal squamous cell carcinoma, ESCC）是我国常见食管癌（esophageal cancer, EC）的主要亚型。虽然ESCC从分子遗传学角度已被广泛研究,但其发病分子机制还没有完全阐明。microRNAs（miRNAs）是一类小的内源性非蛋白编码RNAs,在生理、病理过程中发挥着重要作用,包括细胞分化、凋亡、增殖和代谢。miRNAs通过致癌基因、抑癌基因在ESCC的发病机制中扮演着重要角色。近年来研究表明,许多miRNAs在ESCC组织中的表达存在明显的差异,了解miRNAs及其靶基因在ESCC发生发展中的作用,可能为早期检测、诊断、治疗和预后提供策略。