微小RNA与人类肿瘤

微小RNA(microRNA,miRNA)是一类对基因具有调控功能的内源性非编码小分子RNA.目前认为miRNA在多种生物学过程中起着至关重要的作用,包括细胞增殖、分化、凋亡等.近年研究表明miRNA表达异常能导致疾病甚至肿瘤的发生,有类似于抑癌基因或癌基因的功能.因此,对miRNA的进一步研究为肿瘤的诊断和治疗开辟了...     

微小RNA与人类肿瘤

微小RNA（microRNA,miRNA）是一类对基因具有调控功能的内源性非编码小分子RNA。目前认为miRNA在多种生物学过程中起着至关重要的作用,包括细胞增殖、分化、凋亡等。近年研究表明miRNA表达异常能导致疾病甚至肿瘤的发生,有类似于抑癌基因或癌基因的功能。因此,对miRNA的进一步研究为肿瘤的诊断和治疗开辟了新的路径。     

miR-21过表达与淋巴瘤诊治

微小RNA（microRNA,miRNA）是一类长20~25 nt的非编码RNA,广泛存在真核生物中。miRNA的表达呈现进化保守性、时序性及组织细胞特异性,并参与细胞生长、增殖、分化和凋亡等过程,miRNA的表达与多种肿瘤发病相关,具有肿瘤抑制因子及癌基因的作用。miR-21是在肿瘤中常见的过表达miRNA,在多种肿瘤组织中呈现高表达,其在淋巴瘤中也表达升高,并通过多种方式影响肿瘤抑癌基因及相关信号通路促进淋巴瘤的发生,影响肿瘤的进展及预后。使用转染反义寡核苷酸等分子生物学方法降低miR-21的表达可以抑制肿瘤细胞的生长等生物学的行为并提高肿瘤细胞对化疗的敏感性,深入研究miR-21在淋巴瘤中的作用有望为淋巴瘤的发病机制及治疗等方面提供新的思路。本文对miR-21在淋巴瘤中的表达情况,及其调控因素、作用机制、靶位点及与临床诊断治疗预后的关系进行综述。      

miRNA和转录因子对癌基因的协同调控研究

目的研究癌基因受miRNA和转录因子协同调控的性质。方法 采用累积超几何分布检验计算癌基因在miRNA和转录因子靶基因中的富集情况。结果 癌基因倾向于受到miRNA和转录因子的协同调控;显著协同调控的miRNA和转录因子主要参与转录因子活性、RNA聚合酶II、MAPK信号通路等的调节, 这些生物学过程对于癌症的发生、发展具有重要作用。结论 癌基因的表达倾向于受到miRNA和转录因子的协同调控。     

肿瘤干细胞中异常miRNA的研究进展

微核糖核酸( microRNA,miRNA)是一类内源性非编码单链小RNA,可在转录后调节靶标mRNA的剪切或抑制mRNA翻译.研究发现,miRNA在多种病理生理过程中发挥重要作用,如细胞增殖、干细胞分化、肿瘤形成等.肿瘤干细胞常含有异常的miRNA,其中某些miRNA的异常结构或表达可影响肿瘤发展.根据miRNA表达异常对肿瘤发生、发展的不同影响,可把miRNA分为癌基因性miRNA与抑癌基因miRNA两类.随着对miRNA了解的深入,发现部分miRNA的表达还具有促进和抑制肿瘤的双向性作用.因此,通过区别miRNA对肿瘤干细胞的不同作用,可利用miRNA靶点治疗肿瘤,即利用抗miRNA疗法阻滞癌基因性miRNA;利用miRNA mimics或慢病毒恢复抑癌基因性miRNA的功能,从而抑制肿瘤发展.相信随着miRNA与肿瘤干细胞的特异性及其作用机制等方面研究的深入,miRNA将会作为一种新的肿瘤调控因子,加快肿瘤治疗的研究进展.     

miR-221和miR-222在肿瘤中的研究进展

 由于微小RNA(miRNA)在肿瘤中发挥重要调控作用及其自身特点,使其可能成为基因靶向治疗的有效工具。因此,人们致力于寻找调节关键癌基因或抑癌基因的miRNA。研究发现miR-221及miR-222在多种人类肿瘤中不仅表达异常,而且在不同类型的肿瘤中也发挥着不同的癌基因或抑癌基因样作用,通过调控miR-221和miR-222的表达可能成为肿瘤治疗的有效方法。     

miRNA-148a与肿瘤

0 引言 当今,放化疗及生物靶向治疗已明显提高了肿瘤患者的生存期,但是肿瘤的复发、侵袭转移以及耐药等恶性行为仍是导致治疗失败与死亡的重要原因.microRNA(miRNA)是一类能调控基因表达的非编码蛋白RNA,通过调控mRNA表达和翻译的方式发挥作用.异常表达的miRNA广泛参与肿瘤的发生、发展、侵袭转移及耐药等演进过程.miRNA-148a作为miRNA中的一员,研究发现miRNA-148a在多种肿瘤中表达降低,主要发挥抑癌基因样作用,抑制并逆转肿瘤的恶性表型,其临床价值也越来越受到重视.     

MicroRNA:癌症诊治新靶点

MicroRNA（miRNA）是人类体内重要的转录后调控因子,参与细胞分化、增殖以及凋亡等多个细胞生物学过程。miRNA表达谱的变化与肿瘤的发生发展密切相关,miRNA既可以是癌基因,也可以是抑癌基因。肿瘤的主要生物学特征均涉及到miRNA表达水平的变化,尤其在肿瘤免疫逃逸中的变化十分复杂。循环miRNA是人类血液中一种表达极其稳定的miRNA,能够较准确地反映肿瘤的疾病状态,检测肿瘤患者体内异常的循环miRNA表达谱可能成为肿瘤临床诊断和预后判断的一种新手段。miRNA的检测手段主要包括Northern blotting、微阵列和qRT-PCR等传统方法,也包括二代测序等新兴技术。miRNA模拟物以及携带miRNA的脂质体等治疗方案已取得一定进展,但这些方法均有一定局限性使其无法在临床大规模开展应用。在克服当前的这些技术难点之后,miRNA检测有望进入临床,帮助建立新的肿瘤诊断和治疗方案。     

乳腺癌相关microRNA的研究进展

微小核糖核酸(microRNA,miRNA)是近年来发现的长度约为22个核苷酸(nucleotide,nt)的内源性短链RNA,不编码蛋白质,可通过与编码蛋白质的mRNA互补结合,参与细胞增殖、分化、凋亡等多种重要细胞活动的调控.近年来发现miRNA与肿瘤的发生密切相关,研究表明miRNA可以同时调节多种癌基因或抑癌基因的表达,参与多种恶性肿瘤的演进,是肿瘤发生、发展过程中重要分子.miRNA的发现及其和肿瘤关系的揭示为寻找肿瘤新的生物治疗靶点提供了一个极有希望的研究方向.本文就miRNA在乳腺癌中的相关作用及研究进展作一综述.     

miR-21与肿瘤

MicroRNA（miRNA）是一类具有调控功能的小分子非编码RNA,主要参与基因转录后水平的调控,对生物体的生长、发育、衰老和死亡等生命过程都有着重要的作用。近年来,大量研究结果表明,许多miRNA可作为原癌基因或者抑癌基因,在肿瘤的发生和发展中扮演着重要的角色,其中miR-21最受人重视。大量实验证明在多种肿瘤细胞中,miR-21的表达均出现显著异常,揭示miR-21作为一个致癌miRNA,在多种肿瘤的发生和发展中起着重要的作用。本文综述了miR-21在肿瘤细胞中调控的靶基因及其功能,以及miR-21自身的表达调控机制研究进展,这将为miR-21在肿瘤的诊断、治疗和预后判断中的应用提供重要资料。     

微小RNA研究进展

微小RNA(miRNA)是参与基因转录后水平调控的非编码小分子RNA.人类基因中大约有3%编码miRNAs,而编码蛋白的基因中30%受到miRNAs的调控.miRNAs在多种生物进程中起到关键作用,包括调节发育、细胞增殖、分化和凋亡,相应的miRNAs的表达变化与包括肿瘤在内的多种疾病有关.本文综述miRNAs的生物学及其与肿瘤的联系,并讨论了miRNAs的研究方法.     

The Role of MicroRNA in Chemical Carcinogenesis

MicroRNAs (miRNAs) are important regulators of gene expression. Alteration of miRNA expression caused by exposure of different carcinogens has been well reported. This review aims to present the miRNAs dysregulated by exposure of different types of carcinogens in different biological systems and to discuss their potential roles in different stages of chemical carcinogenesis, following an introduction of miRNA biogenesis, regulatory mechanisms, and target identification. Available information shows that expression of a large number of miRNAs is readily changed by exposure of carcinogens in tissue- and chemical-specific manners. Carcinogenic agents generally induce many more changes in miRNA expression than non-carcinogenic chemicals. There are many more changes in cancer-target tissues than in the non-target tissues after acute or chronic exposure to carcinogens. Many of the miRNAs deregulated by carcinogens are involved in regulation of genes that are important for every stage of chemical carcinogenesis, including xenobiotic metabolism, carcinogen-induced hypomethylation, DNA repair, apoptosis, cell proliferation, tumor suppression, cell transformation, oncogenesis, tumor angiogenesis, tumor progress, mangliant transformation, and other functions. Many miRNAs function as putative oncogenes and tumor suppressor genes. The carcinogenic functions of carcinogens may be dependent on the balance between tumor-suppressor miRNAs and oncogenic miRNAs. Thus, the miRNA profiles and miRNAs specific to carcinogen exposure have the potential to be used as biomarkers for identifying genotoxicity and carcinogenicity of chemicals and indicating exposure of carcinogens.     

ｍｉｃｒｏＲＮＡ与神经胶质瘤的研究进展

ｍｉｃｒｏＲＮＡ（ｍｉＲＮＡ）是近年来发现的一类长度为１９～２５个核苷酸的非编码小分子ＲＮＡ。它主要通过与靶基因ｍＲＮＡ３′ＵＴＲ完全或不完全配对,导致靶标ｍＲＮＡ降解或转录后翻译抑制,从而参与个体发育、细胞凋亡、增殖及分化等生理过程。最近的研究表明,ｍｉＲＮＡｓ可通过调控其靶基因参与的信号通路,调节肿瘤的形成和发展,发挥着类似于癌基因或抑癌基因的功能。多种不同类型的ｍｉＲＮＡｓ在胶质瘤细胞中都有表达,可通过上调或下调相应的ｍｉＲＮＡｓ诱导胶质瘤细胞的凋亡或抑制其增殖。因此,研究胶质瘤细胞ｍｉＲＮＡｓ的表达谱,可能为胶质瘤的诊断和治疗提供新的策略。本文主要对神经胶质瘤ｍｉＲＮＡｓ的表达及其诊断和治疗领域的进展作一综述。     

Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1

MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti-/pre-miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR-7, miR-194 and miR-449b, or overexpressing miR-204, repressed migration, invasion and extracellular matrix-adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR-204, and two binding sites in the 3'-untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR-204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR-204-FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression- and metastasis-related miRNAs offers a novel potential therapeutic strategy for the disease.     

MicroRNA expression profiles distinguish liposarcoma subtypes and implicate miR‐145 and miR‐451 as tumor suppressors

Liposarcomas are rare, heterogeneous and malignant tumors that can be divided into four histological subtypes with different characteristics and clinical behavior. Treatment consists of surgery in combination with systemic chemotherapy, but nevertheless mortality rates are high. More insight into the biology of liposarcoma tumorigenesis is needed to devise novel therapeutic approaches. MicroRNAs (miRNAs) have been associated with carcinogenesis in many tumors and may function as tumor suppressor or oncogene. In this study we examined miRNA expression in an initial series of 57 human liposarcomas (including all subtypes), lipomas and normal fat by miRNA microarrays. Supervised hierarchical clustering of the most differentially expressed miRNAs (p < 0.0002) distinguished most liposarcoma subtypes and control tissues. The distinction between well differentiated liposarcomas and benign lipomas was blurred, suggesting these tumor types may represent a biological continuum. MiRNA signatures of liposarcoma subtypes were established and validated in an independent series of 58 liposarcomas and control tissues. The expression of the miR‐143/145 and miR‐144/451 cluster members was clearly reduced in liposarcomas compared to normal fat. Overexpression of miR‐145 and miR‐451 in liposarcoma cell lines decreased cellular proliferation rate, impaired cell cycle progression and induced apoptosis. In conclusion, we show that miRNA expression profiling can be used to discriminate liposarcoma subtypes, which can possibly aid in objective diagnostic decision making. In addition, our data indicate that miR‐145 and miR‐451 act as tumor suppressors in adipose tissue and show that re‐expression of these miRNAs could be a promising therapeutic strategy for liposarcomas.     

Ischemia caused by time to freezing induces systematic microRNA and mRNA responses in cancer tissue

Time to freezing tumor tissue for RNA expression analysis will always vary to some extent. To evaluate the effect of ischemia time, tumor tissue from ten breast cancer patients was collected and aliquots of tissue were snap frozen at different time points after surgery (0, 0.5, 1, 3 and 6 h). Using miRNA and mRNA expression microarrays and statistical analysis, 56 miRNAs and 1788 mRNAs were found to be significantly altered with ischemia time up to six hours. Several of the 56 miRNAs have been reported to play a role in cancer, such as hsa-miR-663 and hsa-miR-125a-3p. Known stress response genes such as GADD45B, JUND and FOSB were among the mRNAs most significantly affected by time to freezing. A novel statistical method for identification of consistently correlated miRNA–mRNA pairs and miRNA-associated biological processes in time course data is presented. Application of this method revealed that several miRNAs, including hsa-miR-1228, hsa-miR-1225-5p and hsa-miR-574-5p, were associated through their correlation to mRNAs to biological processes such as “response to stimulus” and “stress response”. These miRNAs also showed enrichment of predicted targets among either their positively or negatively correlated mRNAs. The induced miRNAs may play both direct and indirect roles in biological responses. Caution should be taken when the miRNAs and mRNAs reported to be affected by ischemia time are included in a prognostic or predictive signature.