微小RNA-1246靶向糖原合成酶激酶3β激活Wnt/β-连环蛋白信号通路促进前列腺癌细胞的迁移、侵袭和增殖

目的探讨微小RNA(miR)-1246靶向糖原合成酶激酶3β(GSK3β)对前列腺癌(PCa)细胞迁移、侵袭和增殖的作用及分子机制。方法采用miRNA-Seq技术检测PCa组织及癌旁组织中差异表达的miRNA;采用实时荧光定量聚合酶连反应(qRT-PCR)技术检测PCa患者癌组织和血清中miR-1246的表达水平;采用生物信息学分析、荧光素酶报告基因实验、qRT-PCR、蛋白质印迹法分析miR-1246对GSK3β的靶向调控关系。人PCa细胞DU145和LNCaP分别转染miR-1246类似物(mimics)/阴性对照(NC mimics)或miR-1246抑制剂(inhibitor)/阴性对照(NC inhibitor), 通过细胞计数试剂盒(CCK-8)法检测细胞的增殖能力, 通过划痕实验和Transwell迁移实验检测细胞的迁移侵袭能力。两组间比较采用独立样本t检验。结果 miRNA-Seq结果显示, 与癌旁组织比较, PCa组织中有15个miRNA表达显著升高, 51个miRNA表达显著降低, 其中miR-1246在PCa患者组织及血清中表达显著升高(组织:7.93±2.39比...     

miRNA在前列腺癌中的研究进展

前列腺癌(PCa)是男性泌尿系最常见的恶性肿瘤之一,微小RNA(miRNA)是一类内源性的非编码小RNA,研究发现miRNA与PCa的发生和发展密切相关,多种miRNA在PCa中表达异常。本文通过描述miRNA在PCa中表达差异及其与预后的相关性,进一步分析miRNA与放化疗、雄激素受体,以及PCa转移的相关性,来阐明miRNA在PCa发生发展中的的作用。     

microRNA在前列腺癌中的表达及意义

微小核糖核酸(microRNAs,miRNAs)是一类长约22个核苷酸,参与基因转录后水平调控的非编码小分子RNA.最近研究发现了一些在前列腺癌(PCa)组织中有显著表达差异的miRNA,而随着研究的深入,越来越多的研究表明miRNA对PCa的发展、诊断、治疗及预后有着重要的意义.     

miR-34a在前列腺癌血清中的表达意义

目的 探讨血清miR-34a在前列腺癌发生过程中的作用及意义.方法 分别提取20例前列腺癌(PCa)、10例前列腺增生(BPH)及10例健康对照者(N)血清样本的miRNA,应用逆转录-实时定量聚合酶链反应(RT-qPCR)的方法检测三组样本中miR-34a的表达差异,并分析miR-34a的表达与PCa转移是否相关.结果 与健康对照组相比,miR-34a在PCa与BPH患者血清中明显低表达(P均＜0.05),平均下调分别约为7.16、8.53倍.但PCa及BPH的血清中miR-34a的表达水平差异无统计学意义(P＞0.05),并且miR-34a表达水平的高低与PCa是否转移不存在显著相关性(P＞0.05).结论 血清中低表达的miR-34a可能促进了PCa的发生发展,对PCa的诊断及治疗有潜在的临床意义.     

微小循环RNA在鉴别前列腺增生和前列腺癌的有效性分析

目的:有研究表明微小循环RNA(miRNA)在循环中高度稳定,并且可以用作生物标志物以改善疾病诊断和管理。本研究评估4种与前列腺癌(PCa)相关的miRNA鉴别前列腺癌和前列腺增生(BPH)的效果。方法:选取2016年1～12月入我院诊断为PCa患者40例(PCa组),BPH患者40例(BPH组),另外招募30例健康受试者(健康对照组)。逆转录-定量聚合酶链反应用于评估外周血样品中的miRNA表达。结果:与BPH组和健康对照组患者相比,在PCa组患者中观察到miR-15a、miR-126、miR-192和miR-377的表达显著降低(P0.05)。结论:本研究表明这些miRNA在血液循环中的表达可能是有希望的、非侵入性的生物标志物用于检测PCa,但在更大的队列中进一步验证这些结果的临床实施是有必要的。     

miRNA在前列腺癌中的作用及应用进展

前列腺癌(PCa)是世界男性最常见的恶性肿瘤之一,发病率居男性肿瘤第二。PCa的发生发展是基因和环境共同作用的结果,miRNA(MicroRNA)作为mRNA的调节因子,可以调控细胞的增殖、转移和凋亡等过程。研究发现,miRNA的异常表达可作为PCa发生发展、预后的生物标志物,通过抑制蛋白质翻译调控PCa细胞的增殖和转移。本文以miRNA在PCa中的作用以及临床应用价值方面进行综述。     

异常表达的长链非编码RNA与前列腺癌关系的研究进展

前列腺癌(PCa)是全球男性最常见的恶性肿瘤之一,同时也是癌症死亡的常见原因。如今血清标志物的检测已经在很大程度上提高了PCa的早期诊断,然而其潜在的分子机制一直没有完全被人们认识。长链非编码RNA(lncRNA)在PCa中的潜在作用体现在致癌和抑癌两个方面。LncRNA在绝大多数PCa中异常表达。本文将综述lncRNA在PCa中的异常表达,并讨论其在PCa的诊断、预测、预后、转移以及潜在临床治疗方面所扮演的新角色。     

血清miRNA-107检测在前列腺癌诊断与预后判断中的价值

正外周血miRNA作为肿瘤标志物在乳腺癌、肺癌、结直肠癌、前列腺癌等研究中已经取得一定的成果~([1,2])。本研究采用实时荧光定量PCR检测前列腺癌(PCa)患者和前列腺增生(BPH)患者血清miRNA-107的表达水平,研究其对前列腺癌诊断与预后的价值,并分析其与PCa临床病理参数的相关性。材料和方法一、临床资料     

慢性乙型肝炎免疫清除相关微RNA分子的筛选及其生物信息学分析

目的 筛选并分析与慢性乙型肝炎(CHB)免疫清除相关的微RNA(miRNA)分子.方法 连续收集2011年6月至2012年8月江苏省泰州市人民医院住院的12例CHB患者和9名健康体检者,采用miRCURYTM芯片对外周血单个核细胞(PBMC)中miRNA分子的表达差异进行检测,利用生物信息学方法分析差异表达miRNA分子调控的靶基因、分子通路及功能.结果 与健康体检组比较,CHB患者PBMC中存在52个差异表达的微RNA,其中33个上调,19个下调.应用TargetScan、miRBase及miRanda数据库预测上调和下调miRNA分子的靶基因,其中上调miRNA分子调控的靶基因有354个,下凋miRNA分子调控的靶基因1 935个.基因本体(GO)及分子途径(Pathway)分析表明,上调miRNA分子和下调miRNA分子可调控多个分子信号途径,其调控的靶基因具有多种分子功能.miRNA-mRNA网络分析显示,上调的hsa-miR-520d-5p、hsa-miR-106a-5p等和下调的hsa-miR-30a-5p、hsa-miR-29b-3p等可调控多个靶基因,构成复杂的分子网络.结论 CHB患者PBMC存在多个异常表达的miRNA分子,可能通过调控多个靶基因和分子途径,参与CHB的免疫清除.     

核受体NURR1在前列腺癌细胞中的表达及其对环状RNA表达谱的影响

目的 探讨核受体NURR1过表达对前列腺癌(PCa)细胞中环状RNA(circRNA)表达谱的影响,为揭示NURR1相关circRNA分子在PCa进展过程中的作用提供参考。方法 通过UALCAN和TNMplot分析NURR1在PCa中的表达;通过高通量测序分析筛选NURR1过表达的PCa细胞中特征性circRNA分子表达谱;通过GO和KEGG分析差异表达的circRNA分子的功能和参与的信号通路。结果 circ＿0000915在DU145、LNCaP以及PC3细胞中均发生显著的下调表达。在核受体NURR1上调表达的DU145细胞中,1个circRNA上调表达(circ＿0005991),2个circRNA下调表达(circ＿0001460、circ＿0001315);在核受体NURR1上调表达的LNCaP细胞中有2个circRNA显著上调表达(circ＿0040729、circ＿0000722);在NURR1上调表达的PC3细胞中有3个circRNA上调表达(circ＿0001577、circ＿0000854、circ＿0018168),4个circRNA下调表达(circ＿01303...     

MicroRNAs and cancer: Current state and future perspectives in urologic oncology

MicroRNAs (miRNAs) are small non-protein coding RNAs that regulate basic cellular processes and are associated with cancer characteristics. It is the aim of this review to describe the basics of the biogenesis and function of miRNAs, provide their role in tumorigenesis, and demonstrate their clinical potential in general and especially in urologic oncology. For that purpose, a PubMed search up to August 2008 was conducted using the Medical Subject Heading (MeSH) terms for miRNAs alone and the urological carcinomas of kidney, prostate, bladder, testis, and penis combined with the Boolean operator “AND”. Until August 2008, about 3,500 miRNA publications were included in the PubMed database. It has been estimated that about 1,500 would be published in 2008 alone. Several miRNA expression studies and corresponding functional experiments in various cancers showed the important role of miRNAs in cancer initiation and progression and proved their potential as diagnostic, prognostic, and predictive biomarkers and as basis for novel therapeutic strategies. However, in uro-oncology, only a few miRNA related articles (22 for prostate, 4 for kidney, 3 for bladder, and 6 for testis) were published. Cancer-specific expressions of miRNA patterns were shown, but the limited and partly inconsistent data underscore that we are at an early stage regarding this topic in urology. In spite of the obvious significance of miRNAs in malignant tumors, the relatively sparse data on miRNAs in uro-oncology clearly advocate that this area should be more intensively studied. Detailed understanding of the characteristic miRNA abnormalities could contribute to novel approaches in diagnosis and treatment of urological tumors.     

The role of microRNA in castration-resistant prostate cancer

IntroductionCastration-resistant prostate cancer (CRPC) has a historically low median survival rate, but recent advances and discoveries in microRNAs (miRNAs) have opened the potential for new prognostication modalities to enhance therapeutic success. As new chemotherapies and immunotherapies are developed, there is an increasing need for precision and stratification of CRPC to allow for optimization and personalization of therapy.MethodsA systematic literature review was conducted via electronic database resulting in the selection of 42 articles based on title, abstract, study format, and content by a consensus of all participating authors. Most selected articles were published between 2002 and 2013. In this review, we discuss the robustness of miRNAs as a biomarker platform, miRNAs associated with prostate cancer, and recent discoveries of miRNA associations with CRPC.ResultsThe associations discovered have been of interest owing to the ability to differentiate between CRPC and localized prostate cancer. With the evaluation of multiple miRNAs, it is possible to provide a profile regarding tumor characteristics. Furthermore, actions of miRNAs on CRPC tumor cells have the ability to suppress metastatic phenotypes.ConclusionmiRNAs may have a growing role in CRPC prognostication and may potentially transform into a therapeutic potential.     

Five Freely Circulating miRNAs and Bone Tissue miRNAs Are Associated With Osteoporotic Fractures

Osteoporosis as a systemic skeletal disorder is characterized by increased bone fragility and the risk of fractures. According to the World Health Organization, osteoporosis is one of the 10 most common diseases and affects approximately 75 million people in Europe, the United States, and Japan. In this context, the identification of specific microRNA (miRNA) signatures is an important step for new diagnostic and therapeutic approaches. The focus of interest on miRNAs as biomarkers came with new publications identifying free circulating extracellular miRNAs associated with various types of cancer. This study aimed to identify specific miRNAs in patients with osteoporotic fractures compared with nonosteoporotic fractures. For the array analysis, miRNAs were isolated from the serum of 20 patients with hip fractures, transcribed, and the samples were pooled into 10 osteoporotic and 10 nonosteoporotic specimens. With each pool of samples, human serum and plasma miRNA PCR arrays were performed, which are able to identify 83 different miRNAs. Subsequently, a separate validation analysis of each miRNA found to be regulated in the array followed with miRNA samples isolated from the serum of 30 osteoporotic and 30 nonosteoporotic patients and miRNA samples isolated from the bone tissue of 20 osteoporotic and 20 nonosteoporotic patients. With the validation analysis of the regulated miRNAs, we identified 9 miRNAs, namely miR‐21, miR‐23a, miR‐24, miR‐93, miR‐100, miR‐122a, miR‐124a, miR‐125b, and miR‐148a, that were significantly upregulated in the serum of patients with osteoporosis. In the bone tissue of osteoporotic patients, we identified that miR‐21, miR‐23a, miR‐24, miR‐25, miR‐100, and miR‐125b displayed a significantly higher expression. A total of 5 miRNAs display an upregulation both in serum and bone tissue. This study reveals an important role for several miRNAs in osteoporotic patients and suggested that they may be used as biomarkers for diagnostic purposes and may be a target for treating bone loss and optimizing fracture healing in osteoporotic patients. © 2014 American Society for Bone and Mineral Research.     

MicroRNAs: Control and Loss of Control in Human Physiology and Disease

Analysis of the human genome indicates that a large fraction of the genome sequences are RNAs that do not encode any proteins, also known as non-coding RNAs. MicroRNAs (miRNAs) are a group of small non-coding RNA molecules 20–22 nucleotides (nt) in length that are predicted to control the activity of approximately 30% of all protein-coding genes in mammals. miRNAs play important roles in many diseases, including cancer, cardiovascular disease, and immune disorders. The expression of miRNAs can be regulated by epigenetic modification, DNA copy number change, and genetic mutations. miRNAs can serve as a valuable therapeutic target for a large number of diseases. For miRNAs with oncogenic capabilities, potential therapies include miRNA silencing, antisense blocking, and miRNA modifications. For miRNAs with tumor suppression functions, overexpression of those miRNAs might be a useful strategy to inhibit tumor growth. In this review, we discuss the current progress of miRNA research, regulation of miRNA expression, prediction of miRNA targets, and regulatory role of miRNAs in human physiology and diseases, with a specific focus on miRNAs in pancreatic cancer, liver cancer, colorectal cancer, cardiovascular disease, the immune system, and infectious disease. This review provides valuable information for clinicians and researchers who want to recognize the newest advances in this new field and identify possible lines of investigation in miRNAs as important mediators in human physiology and diseases. This work was presented at the Molecular Surgeon Symposium on Personalized Genomic Medicine and Surgery at the Baylor College of Medicine, Houston, Texas, on April 12, 2008. The symposium was supported by a grant from the National Institutes of Health (R13 CA132572 to Changyi Chen).     

microRNA在结肠癌组织的表达及其临床意义

目的 探讨结肠癌组织与对应正常结肠组织miRNA表达特征及其在结肠癌的诊断中的意义.方法 通过定量聚合酶链反应(qRT-PCR)法检测了6对结肠癌及其远端正常结肠的手术标本中200种miRNA的表达情况,并应用PAM分析法探讨miRNA在预测结肠癌病变中的作用.结果 检测6对结肠癌及其远端正常结肠的手术标本中miRNA的表达情况发现在结肠癌组织/远端正常结肠组织中存在132种miRNA,并且有95种miRNA在结肠癌发生过程中表达量发生了显著的变化(变化倍数大于1.5),其中有48种表达增加应用PAM分析方法对9对结肠癌组织/远端正常结肠组织进行了定性判断,发现预测结果 与病理切片诊断结果 一致.结论 miRNA与结肠癌的发展有着密切的联系,并且其可以作为一个有效的肿瘤标志物以进行结肠癌的早期预测和诊断.     

Combination of three miRNA (miR-141, miR-21, and miR-375) as potential diagnostic tool for prostate cancer recognition

Purpose

Prostate cancer (PCa) is a common tumor disease in western countries and a leading cause of cancer-driven mortality in men. Current methods for prostate cancer detection, like prostate-specific antigen screening, lead to significant overtreatment. The purpose of the study was to analyze circulating microRNAs in serum as non-invasive biomarkers in patients with diagnosis of prostate cancer and healthy individuals.

Methods

This preliminary study included a population of 20 patients with mean age of 68.6 years and mean PSA of 21.3 ng/ml. Eight healthy patients were used as control. MiRNAs were quantified in the total RNA fraction extracted from serum and levels of five microRNAs (miR-106b, miR-141, miR-21, mir-34a, and miR-375) were quantified by RT-qPCR. Statistical analyses evaluated correlation between clinicopathological data and miRNAs expression levels.

Results

Relative expression ratios of miR-106b, miR-141-3p, miR-21, and miR-375 were significantly increased (1.8-, ?1.9-, 2.4-, and 2.6-fold, respectively) in the PCa group compared to healthy control. Using receiver operating characteristics, the highest area under the curve equal to 0.906 was obtained for miR-357 and indicates a very good diagnostic properties of this biomarker. We found expression level of mir-34a not related with PCa.

Conclusions

Our results support previous findings on the possibility of discriminating prostate cancer patients from healthy controls by detecting miRNA (miR-141-3p, miR-21, and miR-375). Further insights into miRNA abundance and characteristics are necessary to validate the panel of miRNA as surrogate markers in diagnosis of prostate cancer.

     

MicroRNAs and their potential for translation in prostate cancer

ObjectivePatients die of prostate cancer (CaP) because predictably after a period of response to androgen withdrawal, their CaP becomes castrate resistant. In this paper, we discuss the role that microRNAs (miRNAs) may play in this process.MethodsmiRNAs are a group of endogenous, small non-coding RNA molecules that are thought to be responsible for the regulation of up to 30% of gene expression. The miRNA expression profile between androgen responsive and castrate resistant CaP cell lines is compared. Functional studies were carried out to identify the importance of the miRNA targets in controlling this process.ResultsThere were 17 differentially expressed miRNAs found, 10 up-regulated and 7 down-regulated. Among these, miRNA-125b was found to have the ability of rendering LNCaP cells resistant to androgen withdrawal. It was found to be androgen regulated and one of its targets, BAK1, was identified as being involved in how these CaP cells undergo apoptosis functionally.ConclusionmiRNA-125b, at least in the CaP cell lines tested, is involved in the development of castrate resistance. While clearly this miRNA is only part of the answer, miRNAs may lead us in a new direction in trying to solve the central problem in CaP.