微小RNA-30a:肿瘤治疗的潜在靶点

微小RNA(miRNA)是长约20~25个核苷酸的内源性非编码RNA,主要通过抑制mRNA翻译和诱导mRNA降解而调节靶基因的表达,人类大约30%的基因受miRNAs调节。研究发现,大量miRNAs在肿瘤中表达失调,常常引起多种重要过程的紊乱,包括细胞增殖、侵袭与转移、凋亡以及耐药等。在肿瘤的发生过程中,不同的miRNA可能起着类似抑癌基因或者癌基因的作用,参与调节肿瘤细胞发生、发展等过程。miR-30a是miRNA的成员之一,通过调节靶基因的表达,参与调控肿瘤细胞增殖、转移和凋亡等过程。不同肿瘤血清中miR-30a的表达水平对肿瘤的早期诊断、治疗以及预后判断有着重要作用。此外,miR-30a的表达失调还与抗肿瘤药物耐药性的产生密切相关,推测其有望成为肿瘤治疗的一个潜在新靶标。本文就近年来miR-30a在肿瘤中作用的最新研究进展作一综述。     

miR-21与肿瘤研究进展

目的:总结国内外关于miR-21与肿瘤发生机制、肿瘤诊断、治疗、预后的研究进展。方法:以"microRNA、miR-21、肿瘤和靶基因"为关键词,应用PubMed及CNKI期刊全文数据库检索系统,检索2000-01-2011-11的相关文献,共检索到英文文献126篇,中文文献62篇。纳入标准:1)miR-21在肿瘤发生发展中的作用机制;2)miR-21已证实的部分靶基因的功能;3)miR-21在肿瘤的诊断、治疗和预后中的作用。排除与本研究无关的文献,最终纳入分析29篇文献。结果:miR-21的基因定位决定了其与肿瘤的发生发展密切相关;部分靶基因如pdcd4、pten和tpm1参与肿瘤细胞的增殖、分化和凋亡、血管浸润和转移等生物学过程,因此检测miR-21表达变化可作为肿瘤诊断、治疗和预后的重要生物学指标。结论:miR-21与多种肿瘤的发生发展密切相关,未来可作为肿瘤诊断,治疗和预后的重要生物学指标。     

miR-149与肿瘤关系的研究进展

miRNAs是一类长度约为20~25个核苷酸,参与基因调控表达的内源性非编码RNA。miR-149作为miRNAs的重要成员,在多种肿瘤中表达异常,其表达水平与肿瘤细胞增殖、转移、凋亡、耐药、患者的早期诊断及预后密切相关。因此,miR-149有望成为新一类抗肿瘤治疗的靶点。     

microRNA-196a与肿瘤相关性的研究进展

microRNA-196a(miR-196a)作为miRNA家族中的成员之一,近年来受到了广泛关注。miR-196a不但在多种生物学过程中起重要的调控作用,同时还有研究表明在肿瘤的发生发展中miR-196a还发挥类似癌基因的功能。研究发现,miR-196a在肿瘤患者的血清、组织及细胞中呈高表达,而且能够促进肿瘤细胞增殖、侵袭及转移,抑制肿瘤细胞凋亡,增强肿瘤耐药性。本文结合国内外最新报道对miR-196a与肿瘤相关性研究进展做一综述。     

miR-196a 在肿瘤研究中的进展

最近研究表明,miR-196a在多种肿瘤的发生、发展中发挥类似癌基因的生物学功能,降低miR-196a的表达可抑制肿瘤细胞的增殖、侵袭及转移,促进肿瘤细胞凋亡,逆转肿瘤耐药。miR-196a有望成为肿瘤早期诊断、预后预测及逆转耐药的重要新靶标。本文结合国内外最新报道对miR-196a与肿瘤相关性研究进展作一综述。     

miR-10a在肿瘤中的研究进展

miR-10a作为微小RNA（miRNA）家族的成员之一,属于miR-10家族,定位于17号染色体短臂的HOXB4与HOXB5基因之间.miR-10a在多种人体肿瘤中异常表达,与肿瘤的发生、发展及预后密切相关.文章就miR-10a与多种肿瘤的关系进行综述.     

miR-26a靶向MMP16参与调控胃癌细胞侵袭作用研究

背景与目的：胃癌发生侵袭转移是导致患者预后不良的重要因素。本研究旨在明确miR-26a在调控胃癌细胞运动侵袭中的作用及其可能机制。方法：通过实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)检测胃癌组织细胞中miR-26a表达情况,体外通过CCK-8法、平板克隆形成实验和Matrigel-Transwell实验评价miR-26a对人胃癌细胞增殖、运动和侵袭能力的影响。荧光素酶报告基因系统评估miR-26a对下游靶基因的调控作用。结果：胃癌组织中miR-26a表达较癌旁组织明显下降。miR-26a体外对胃癌细胞增殖无明显影响,但可显著抑制胃癌细胞的运动和侵袭。相反,抑制miR-26a表达可促进胃癌细胞的侵袭能力。生物信息学分析提示,基质金属蛋白酶16(matrix metalloproteinase 16,MMP16)为miR-26直接调控靶基因,miR-26a可抑制胃癌细胞MMP16 miRNA和蛋白的表达。荧光素酶报告基因检测提示,miR-26a可与MMP16 mRNA 3’UTR结合诱导其转录后抑制。进一步研究提示,MMP16 siRNA对胃癌细胞侵袭具有模拟miR-26a作用,而过表达MMP16可拮抗miR-26a对胃癌细胞侵袭的影响。结论：miR-26a可通过靶向MMP16来抑制胃癌细胞运动侵袭,miR-26a可作为抑制胃癌细胞侵袭的重要干预靶点。     

miR-100与肿瘤关系的研究进展

miR-100既可表现出致癌基因的作用,又可表现出抑癌基因的作用,其不仅在多种肿瘤（宫颈癌、前列腺癌、膀胱癌和肺癌等）的发生、发展中发挥重要作用,而且还可增加肿瘤细胞对化疗药物的敏感性。miR-100有望成为肿瘤治疗的新靶点及预测预后的新分子标记。本文结合国内外最新报道对miR-100与肿瘤相关性的研究进展作一综述。     

miR-193b与肿瘤相关性的研究进展

miRNAs已被证实是基因表达的关键调控因子,不同水平的表达与各种疾病相关。大多数的研究表明,miRNAs表达谱中的miR-193b参与机体多种病理生理过程,在肿瘤发生、发展过程中发挥抑癌基因的作用,可抑制肿瘤细胞增殖、迁移和侵袭能力。因此,miR-193b在疾病的诊断、治疗和预后评估等方面将会发挥更大的作用,有着广阔的应用前景。本文就miR-193b与肿瘤相关性研究进展作一综述。     

微小RNA-320在肿瘤中的研究进展

微小RNA（miRNAs）是一类细胞内源性表达的小分子非编码RNA,具有转录后调控基因表达的作用。近年来,在结肠癌、乳腺癌和胆管癌等多种肿瘤中发现miR-320表达下调,提示miR-320可通过抑制细胞增殖和侵袭等方式抑制肿瘤进展。对于miR-320调控的靶基因及相关信号通路的深入研究,有助于阐明肿瘤发生发展的分子机制,并有望为临床肿瘤治疗提供新的靶点。本文就miR-320在肿瘤中的研究进展作一综述。     

Serum miR-26a as a diagnostic and prognostic biomarker in cholangiocarcinoma

In order to determine the diagnostic and prognostic value of miR-26a in Cholangiocarcinoma (CCA), we compared miR-26a levels in serum from 66 CCA patients and 66 healthy controls, which was followed by serum analysis between the pre-operative serum and post-operative serum of these CCA patients. We found the concentration levels of miR-26a in serum of CCA patients were significantly higher than that from healthy controls (P < 0.01). Furthermore, the concentration levels of miR-26a in the post-operative serum were significantly reduced when compared to the pre-operative serum (P < 0.001). High miR-26a in serum was correlated significantly with clinical stage, distant metastasis, differentiation status, and poor survival of CCA patients. More importantly, serum miR-26a was an independent prognostic marker for CCA. In conclusion, our results suggested that miR-26a in serum might be a potential and useful noninvasive biomarker for the early detection of CCA.     

MicroRNA-26a promotes anoikis in human hepatocellular carcinoma cells by targeting alpha5 integrin

Metastasis is the major reason for the death of patients suffering from malignant diseases such as human hepatocellular carcinoma (HCC). Among the complex metastatic process, resistance to anoikis is one of the most important steps. Previous studies demonstrate that microRNA-26a (miR-26a) is an important tumor suppressor that inhibits the proliferation and invasion of HCC cells by targeting multiple oncogenic proteins. However, whether miR-26a can also influence anoikis has not been well established. Here, we discovered that miR-26a promotes anoikis of HCC cells both in vitro and in vivo. With a combinational analysis of bioinformatics and public clinical databases, we predicted that alpha5 integrin (ITGA5), an integrin family member, is a putative target of miR-26a. Furthermore, we provide experimental evidence to confirm that ITGA5 is a bona fide target of miR-26a. Through gain- and loss-of-function studies, we demonstrate that ITGA5 is a functional target of miR-26a-induced anoikis in HCC cells. Collectively, our findings reveal that miR-26a is a novel player during anoikis and a potential therapeutic target for the treatment of metastatic HCC.     

MicroRNA-27a distinguishes glioblastoma multiforme from diffuse and anaplastic astrocytomas and has prognostic value

MicroRNAs (miRNAs) are a class of small noncoding RNAs that bind to 3’-untranslated (UTR) regions of target messenger RNAs to regulate protein synthesis. Reports have suggested that a set of specific miRNAs may be used as diagnostic and/or prognostic markers for astrocytoma grading. However, there are few studies of the specific miRNAs differentially expressed in each astrocytoma grade. MiRNA-containing total RNA was isolated from archived formalin-fixed, paraffin-embedded (FFPE) samples from WHO grade II-IV astrocytoma patients. The RNA was labeled and hybridized to Affymetrix miRNA 2.0 arrays. Statistical analysis identified several miRNAs differentially expressed in each astrocytoma grade. In particular, miR-27a, miR-210, and miR-1225-5p expression levels were able to differentiate grade IV from grade II and III astrocytomas as confirmed by real-time PCR. Kaplan-Meier survival analysis showed that disease progression occurred faster for Glioblastoma Multiforme (GBM) patients with a lower miR-27a expression level. Transfection of CRL-1690 GBM human cancer cells with a miR-27a oligonucleotide inhibitor followed by Real-time PCR identified six potential miR-27a target genes. Furthermore, the miR-27a oligonucleotide inhibitor induced CRL-1690 cell apoptosis. Taken together, our results provide additional miRNA signatures for distinguishing GBM from lower astrocytoma grades and suggest miR-27a as a prognostic and therapeutic target for GBM.     

MicroRNA-19a and -19b regulate cervical carcinoma cell proliferation and invasion by targeting CUL5

MicroRNAs (miRNAs) play a key role in the regulation of gene expression. In this study, we demonstrate that microRNA-19a and -19b (miR-19a/b) are highly expressed in human cervical cancer cells and are involved in maintaining the malignant phenotypes of HeLa and C33A cells. Up-regulation of miR-19a and miR-19b promoted cell growth and invasion, whereas knockdown of miR-19a and miR-19b yielded the reverse phenotype. CUL5 was identified as a novel target gene of both miR-19a and miR-19b. CUL5 ectopic over-expression without its 3' untranslated region (UTR) abolished the effect of miR-19a/b on HeLa and C33A cell proliferation and invasion. These results indicated that miR-19a/b directly and negatively regulate CUL5 expression in cervical cancer cells, highlighting the importance of miR-19a and miR-19b and their target genes in tumorigenesis.