胃癌转移相关微小RNA的研究进展

胃癌是我国最常见的恶性肿瘤之一,复发和转移仍就是胃癌治疗的一大难题.微小RNA(miRNA)是一类内源性非编码小RNA,在转录后水平对基因表达进行负调控.可以作为一类新型的癌基因或抑癌基因参与肿瘤的凋亡,生长,侵袭.研究miRNA对胃癌转移发生发展的作用有助于我们寻找治疗胃癌的新方法.本文就miRNA和胃癌转移关系的研究进展做一综述.     

miRNA-200 家族在卵巢癌中作用的研究进展

MicroRNA(miRNA)是一类非编码小分子RNA,参与基因转录后水平调控,与肿瘤的形成、侵袭及转移、治疗及预后过程密切相关。研究发现,miRNA-200家族包括miR-141、miR-200a、miR-200b、miR-200c和miR-429在卵巢癌中的表达改变明显,且参与卵巢癌的发生、侵袭转移、卵巢癌细胞对紫杉醇的敏感性及复发过程,可能是用于卵巢癌的早期诊断、治疗、预后预测的指标。本文主要对miRNA-200家族在卵巢癌中的研究进展进行综述。     

MiRNA调控非小细胞肺癌转移的研究进展

微小RNA是内源性的非编码小RNA分子,通过与靶mRNA的结合在转录后水平调控基因的表达,从而参与众多生命活动的调控。NSCLC是严重威胁人类健康的恶性肿瘤,侵袭转移是其主要特征,也是其治疗失败和死亡的主要原因。miRNA可以通过促进上皮-间质转化、金属基质蛋白酶表达,以及血管生成来促进NSCLC转移,而且miRNA在调节肺癌干细胞特性中也发挥着重要作用。转移相关的miRNA已成为肺癌靶向治疗的新靶点。     

微小RNA-29与恶性肿瘤

miR-29家族是人类重要的miRNA分子,在多数恶性肿瘤中扮演抑癌RNA分子的作用,因而呈现低表达水平,它通过上调抑癌基因表达及调控相关肿瘤信号通路等机制,抑制恶性肿瘤的增殖、分化、侵袭和转移。miR-29家族不仅能作为恶性肿瘤治疗的靶点,而且在肿瘤的诊断及预后评估方面具有重要价值。     

长链非编码RNA与宫颈癌

长链非编码RNA(long noncoding RNA,lnc RNA)是一类长度超过200个核苷酸、无蛋白编码功能的一类RNA分子。Lnc RNA在人类肿瘤发生中发挥着重要作用,可在表观遗传学、转录及转录后水平调控基因表达,影响肿瘤的发生、发展,并且与肿瘤侵袭、转移及患者预后有一定关系。近年研究表明,lnc RNA在宫颈癌中异常表达,发挥着癌基因或抑癌基因活性,可成为宫颈癌分子诊断和基因治疗的新靶点。该文就lnc RNA在宫颈癌中的最新研究进展作一综述。     

miR-451与人类肿瘤关系的研究进展

Micro RNAs(miRNA)是一类在转录后水平调控基因表达的小分子非编码RNAs,通过调节细胞的增殖、分化、凋亡使机体维一个动态平衡。近年来,大量研究表明许多miRNA可作为原癌基因或者抑癌基因参与肿瘤的发生、发展,进一步研究发现,通过检测和调控这些miRNA,可用于肿瘤的早期诊断和治疗。最近一系列研究发现miRNA-451(miR-451)在许多肿瘤中存在差异性表达,与这些肿瘤的发生、发展、治疗有着密切的联系。本文对人类肿瘤中miR-451表达、调控的相关研究做一综述,为miR-451在肿瘤的诊断、治疗及预后中的应用提供重要资料。     

miRNA-125家族与肿瘤关系的研究进展

miRNA-125家族是由在进化上高度保守的miRNA-125a-3p、miRNA-125a-5p、miRNA125b-1、miRNA-125b-2组成,其表达紊乱与肿瘤的发生与发展密切相关。miRNA-125家族的下游靶点包括转录因子如STAT3、细胞因子(如IL-6,TGF-β)、相关蛋白(如抑癌蛋白p53、促凋亡蛋白Bak1、RNA结合蛋白Hu R)等。miR-125家族参与调控这些靶点进而影响肿瘤的发生发展。现主要总结了miRNA-125家族及其靶基因在抑制与促进肿瘤发生、发展方面的双重作用,并从增殖、凋亡、侵袭与转移和免疫反应等4个方面详细阐述了其作用机制。     

微RNA参与调控肿瘤血管生成

肿瘤血管生成是由多种因子参与调控的复杂过程,对肿瘤的生长、侵袭和转移起着关键作用.微 RNA(microRNA, miRNA)是一段长约22 nt的非编码RNA序列,参与调节细胞增殖、分化、凋亡,肿瘤发生、发展等多种生命活动.认识miRNA与肿瘤血管生成的关系不但能加深对血管生成分子机制的理解,同时对阐明 miRNA的功能具有重要意义.     

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。     

miRNA-126对多种肿瘤发生发展的影响及其作用机制的探讨

miRNA是一类高度保守的非编码RNA,其作为一种重要的转录后基因调控元件,在肿瘤的发生发展过程中发挥重要的作用。miRNA-126被认为是一种肿瘤抑制因子,对多种肿瘤的增殖、迁移、侵袭及预后具有显著的抑制作用。本文主要对miRNA-126在肿瘤方面的研究新进展作一综述。     

HeLa细胞中miRNA-214靶基因Mek3的确定

目的探索miRNA-214在HeLa细胞中的与其靶基因Mek3相互作用。方法通过miRNA靶基因预测网站寻找可能与miRNA-214相互作用的靶基因,合成miRNA-214和对照序列,将miRNA-214、对照序列、Mek3的3’非翻译区（3’UTR）以及突变的Mek3 3’UTR分别克隆到表达载体上,转染HeLa细胞,转染48h后提取蛋白,检测绿色荧光蛋白的表达水平;HeLa细胞转染miRNA-214后,Trizol抽提RNA,通过荧光定量PCR检测Mek3mRNA的表达水平;Western印迹检Mek3的蛋白表达水平。经过以上实验从mRNA和蛋白水平上验证了在HeLa细胞中miRNA-214对靶基因Mek3的作用效应。结果生物信息学方法显示miRNA-214和Mek3存在可能的结合位点。经过实验验证了miRNA-214可以下调Mek3的mRNA和蛋白水平。结论miRNA-214可以负调节靶基因Mek3的表达。     

Chemoresistance in ovarian cancer linked to expression of microRNAs

Abstract

We evaluated the differential expression of several microRNAs (miRNAs) among malignant cells in ascites and matched omental metastasis in patients with epithelial ovarian cancer (EOC). Ascites and omental tumors were collected prospectively from five patients who were undergoing primary surgical cytoreduction. Patient samples were processed and treated with carboplatin, paclitaxel and combination chemotherapy. Cell viability was evaluated and miRNA profiling was performed on both tumor cells from ascites fluid and omental cake. Quantitative real-time PCR (RT-q-PCR) and western blots were used to evaluate expressions of miRNA-21 and miRNA -214 and associated proteins. Malignant cells in ascites showed greater cell viability when treated with carboplatin compared to omental metastasis. A significant up-regulation of miRNA-21 and miRNA-214 was observed in malignant cells of ascites compared to omental metastasis; this was confirmed by both cell viability assay and RT-q-PCR. Ours is the first report that demonstrates significant up-regulation of miRNA-21 and miRNA-214 in tumor cells from ascites of patients with EOC compared to omental metastasis. This finding has important implications for intrinsic carboplatin resistance in these patients.     

High-Throughput miRNA and mRNA Sequencing of Paired Colorectal Normal,Tumor and Metastasis Tissues and Bioinformatic Modeling of miRNA-1 Therapeutic Applications

MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are, so far, hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We validated six miRNAs in a large tissue screen containing 16 additional tumor entities and identified miRNA-1, miRNA-129, miRNA-497 and miRNA-215 as constantly de-regulated within the majority of cancers. Of these, we investigated miRNA-1 as representative in a systems-biology simulation of cellular cancer models implemented in PyBioS and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system, miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options.     

miRNA表达谱与上皮性卵巢癌

Micro RNA(miRNA)是近年来研究发现的一种高度保守,长度大约19-25个核苷酸的非编码小分子RNA,起着调控基因表达的作用。目前认为miRNA能调控细胞周期、凋亡、分化、发育和新陈代谢等,参与肿瘤的发生与发展,因此异常表达的miRNAs表达谱有可能成为一种全新的肿瘤分子标记物。相关研究表明,miRNA能够以一种被保护的状态存在于血清及血浆中,因此miRNA表达谱的发现具有易检测性、重现性以及非侵袭性。研究显示血清及血浆中miRNA表达谱可作为上皮性卵巢癌生物信号分子,在上皮性卵巢癌早期诊断、预后判断和化疗药物应用等方面具有不可替代的作用。本文将对miRNA表达谱与上皮性卵巢癌的关系进行一个简单总结。     

miRNA-105在胃癌组织中的表达情况

目的:分析胃癌组织与癌旁正常胃黏膜组织中miRNA的差异表达情况。方法:收集胃癌组织和其相应癌旁正常胃黏膜组织共33对,经抽提、纯化RNA后,反转录合成荧光分子Hy3的cDNA探针,将其与miRCURYTMLNA Array(v.16.0)(Exiqon公司)芯片进行杂交,应用Axon GenePix 4000B芯片扫描仪来扫描miRNA芯片的荧光强度,GenePix Pro 6.0软件(Axon)把图像转化为数字信号,以差异大于2倍的为标准来确定胃癌黏膜组织中差异表达的miRNA。再用实时荧光定量PCR方法验证芯片结果中表达异常增高的miR-105在33例胃癌组织中的表达情况。结果:miRNA表达谱芯片结果显示:胃癌组织共中有51种miRNA表达异常,其中miR-105、miR-548n、miR-214*、miR-4309等31种miRNA表达上调,miR-31、miR-1275、miR-26b*、miR-744等20种miRNA表达下调;实时荧光定量PCR证实与癌旁正常胃黏膜组织相比,胃癌组织中miR-105表达显著上调(P0.01)。结论:miR-105在胃癌组织的表达明显高于正常胃黏膜组织,可能与胃癌的发生、发展相关。我们的研究为胃癌的发病机制和诊断治疗提供了一个新的研究方向。     

miRNA参与肿瘤基因表达调控研究进展

调查表明,我国城乡居民恶性肿瘤死亡率属于世界较高水平,而且呈持续的增长趋势。近年来的研究发现在肿瘤的发生与发展过程中涉及到多种因素,其中mi RNA可能扮演了重要的作用。mi RNA是一种长度约为22 nt的非编码短序列RNA,通过介导特异性的基因沉默导致靶m RNA降解,促使相应蛋白质的转译受阻而失去原有编码蛋白质的功能。mi RNA在细胞分裂周期中影响着基因的表达调控,在此过程中基因表达的失控就可能导致疾病的发生。而肿瘤的发生是以细胞恶变为基础,细胞恶变则是与细胞周期调控因素失衡相关,由此提示了一些mi RNA可能参与了肿瘤的发生、发展过程并在其中发挥了重要作用。随着研究的深入,mi RNA逐渐成为肿瘤诊治的新研究方向。本文主要讨论mi RNA在肿瘤基因表达调控方面的研究进展。     

Clinical significance of the expression of miRNA-21, miRNA-31 and miRNA-let7 in patients with lung cancer

ObjectiveTo explore the expression differences of miRNA-21, miRNA-31 and miRNA-let7 between lung cancer patient and healthy people, thereby providing reference for early diagnosis of lung cancer.MethodReal-time PCR was employed to determine the expression difference between lung cancer patients (50 cases) and healthy people (24 cases). The clinical data of lung cancer patients were analyzed to explore the correlation between clinicopathological characteristics and expression level of miRNA-21, miRNA-31, miRNA-let7.ResultsThe relative expression levels of miRNA-21 and miRNA-31 in lung cancer group were obviously higher than those in healthy control group, and the relative expression level of miRNA-let7 in lung cancer group was slightly higher than that in healthy control group. Lung cancer patients with lymph node metastasis had higher expression level than those without lymph node metastasis. The ROC curve showed that the three miRNAs had clinical diagnosis efficiency for lung cancer, and the combined detection of the three miRNAs were more efficient in diagnosing lung cancer. Survival curve analysis suggested that the median survival times of patients in the miRNA-21 and miRNA-31 high expression groups were shorter than those in the low expression groups, and the median survival time of patients in miRNA-let7 high expression group was longer than that in the low expression group.ConclusionPlasma miRNA-21, miRNA-31 and miRNA-let7 may be diagnostic marker for lung cancer.     

血清miRNA-93、miRNA-223联合miRNA-324-3p可作为诊断PCOS的生物标记物

本研究拟基于最近的miRNA报道,结合前期关于肌肉生长抑素(myostatin, MSTN)的相关研究,探究多囊卵巢综合症(ploycystic ovary syndrome, PCOS)患者血清miRNA和生长抑素的表达及其相关临床病理特征。本研究选取160例在湘南学院附属医院妇科就诊的女性为研究对象,通过PCR、ELISA等方法比较PCOS患者血清miRNA和生长抑素的表达情况,并且分析其相关临床病理特征。结果显示,通过PCR的方法发现mi RNA-93、mi RNA-223在PCOS患者的血清中显著升高,而mi RNA-4522、mi RNA-6767-5p和mi RNA-324-3p则表达下降。本研究建立了3个miRNA的预测模型,并证实预测模型在筛选组和验证组中有很好的敏感性和特异性,可以有效区分PCOS患者和正常人群,但研究结果也发现,miRNA模型结合MSTN没有更好的诊断价值。