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Hafez MM Hassan ZK Zekri AR Gaber AA Al Rejaie SS Sayed-Ahmed MM Al Shabanah O 《Asian Pacific journal of cancer prevention》2012,13(2):591-598
Aim and background: MicroRNAs (miRNAs) are a class of naturally occurring small noncoding RNAs that regulate gene expression, cell growth, differentiation and apoptosis by targeting mRNAs for translational repression or cleavage. The present study was conducted to study miRNAs in Egyptian breast cancer (BC) and their relation to metastasis, tumor invasion and apoptosis in addition to their association with the ER and PR statuses. Methods: Real Time RT-PCR was performed to identify the miRNA expression level of eight miRNAs and eight metastatic-related genes in 40 breast cancer samples and their adjacent non-neoplastic tissues. The expression levels of each miRNA relative to U6 RNA were determined using the 2–ΔCT method. Also, miRNA expression profiles of the BC and their corresponding ANT were evaluated. Results: The BC patients showed an up-regulation in miRNAs (mir-155, mir-10, mir-21 and mir-373) with an upregulation in MMP2, MMp9 and VEGF genes. We found down regulation in mir-17p, mir-126, mir-335, mir-30b and also TIMP3, TMP1 and PDCD4 genes in the cancer tissue compared to the adjacent non-neoplastic tissues. Mir -10b, mir -21, mir-155 and mir373 and the metastatic genes MMP2, MMP9 and VEGF were significantly associated with an increase in tumor size (P < 0.05). No significant difference was observed between any of the studied miRNAs regarding lymph node metastasis. Mir-21 was significantly over-expressed in ER-/PR- cases. Conclusion: Specific miRNAs (mir-10, mir-21, mir-155, mir-373, mir-30b, mir-126, mir-17p, mir-335) are associated with tumor metastasis and other clinical characteristics for BC, facilitating identification of individuals who are at risk. 相似文献
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microRNAs(miRNAs)是一类长约21~24个核苷酸的小分子非编码RNA,通过与位于靶基因mRNA 3' UTR区域的特异性结合位点互补配对结合,促进靶基因mRNA的降解和/或抑制翻译过程,从而行使调节基因表达的功能。miRNAs广泛存在于真核细胞内,参与了细胞的分化、增殖、凋亡、周期调控、迁移以及肿瘤的发生发展等多种生物学进程。miRNAs表达谱是一类潜在的强有力的评估肿瘤发生、发展、诊断、治疗及预后的生物学指标,在人类肿瘤的不同类型中均存在显著差异。乳腺癌是女性最常见的恶性肿瘤之一,不同类型的乳腺癌组织中miRNAs的表达谱也不同。本文对目前为止发现的一些与乳腺癌发生发展、转移及治疗反应等相关的miRNAs及其下游靶基因在乳腺癌中的表达及作用进行综述。 相似文献
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EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy 总被引:15,自引:0,他引:15
Osta WA Chen Y Mikhitarian K Mitas M Salem M Hannun YA Cole DJ Gillanders WE 《Cancer research》2004,64(16):5818-5824
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Triple negative breast cancer is a very aggressive subtype of breast cancer characterized by high recurrence rates and a greater likelihood of death compared to other breast cancers. Additionally, it is characterized by lack of expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2)/neu. The current treatment for triple negative breast cancer is chemotherapy and that often results in a poor outcome. Therefore, it is essential that new, alternative therapeutic targets are identified. MicroRNAs are small non-coding elements that regulate the expression of various genes. Research has identified microRNAs promoting and in some cases suppressing cell proliferation by targeting genes in triple negative breast cancer cells. Thus, they are promising cancer targets and they should be further investigated as they could function as biomarkers of triple negative breast cancer in the future. Here we focus on the role of microRNAs in triple negative breast cancer and their potential as therapeutic targets. 相似文献
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微小RNAs(MicroRNAs,简称miRNAs)是长度为18~25个核苷酸的内源性非编码小分子RNA,通过剪切mRNA、调节靶基因、抑制蛋白质翻译,进而调控多种生物学行为,如发育进程、干细胞分化、细胞凋亡、疾病以及肿瘤的发生。本文将介绍miRNAs作为原癌基因或抑癌基因参与人类乳腺癌发生、发展及扩散转移的研究进展,并对人类现有miRNAs作为肿瘤基因诊治的应用情况作一简述。 相似文献
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目的:分析miR-653在乳腺癌细胞及肿瘤组织中的表达变化,研究其对乳腺癌细胞生物学行为的影响,揭示其在乳腺癌中发挥的作用及其相关作用机制。方法:采用qRT-PCR比较miR-653在正常组织、细胞和乳腺癌组织、乳腺癌细胞系中的表达水平;采用CCK8法和Tranwell检测miR-653对细胞的增殖、迁移能力的影响;采用qRT-PCR和Western blot检测NFKBIB在正常组织、细胞和乳腺癌组织、乳腺癌细胞系中的表达水平;采用CCK8法、流式细胞法和Tranwell检测miR-653和NFKBIB对乳腺癌细胞增殖、细胞周期、迁移能力的影响;Western blot检测miR-653对NFKBIB、p65、Livin和Survivin蛋白表达的影响。结果:发现miR-653在乳腺癌肿瘤组织和乳腺癌细胞株中表达明显升高,可以促进乳腺癌细胞的增殖、迁移能力;NFKBIB是miR-653的靶基因,miR-653可以负性调控NFKBIB的mRNA和蛋白表达;转染miR-653可以促进细胞的增殖、迁移能力以及诱导S期阻滞,过表达NFKBIB可以逆转这种促进效果;miR-653可以通过调控NFKBIB激活NF-κB通路调节其下游蛋白Livin和Survivin的表达。结论:本研究揭示了miR-653通过抑制靶基因NFKBIB的表达激活NF-κB,促进乳腺癌细胞的增殖、迁移以及诱导S期阻滞,在乳腺癌中发挥促癌因子的作用。因此miR-653具有成为乳腺癌诊断及治疗新靶点的潜力。 相似文献
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Expression of microRNAs (miRNAs) has been found to be deregulated in all human cancers, where they may behave either as oncogenes or as tumor-suppressor genes. In the last 5 years, miRNA investigations in breast cancer represented an exciting area of discovery, which produced new knowledge on the molecular basis of this disease, tools for molecular classification, and new markers with diagnostic and prognostic relevance, as well as the discovery of novel breast cancer-predisposing genes. In this review, we describe current knowledge of the role of microRNAs in breast cancer. 相似文献
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Chen C Zhou Z Ross JS Zhou W Dong JT 《International journal of cancer. Journal international du cancer》2007,121(1):80-87
The amplification of the q21 band of chromosome 8 (8q21) occurs in a large percentage of breast cancers. WWP1, an HECT domain-containing ubiquitin E3 ligase located in the 8q21 region, negatively regulates the TGF-beta tumor suppressor pathway. To characterize the role of WWP1 in breast cancer, we analyzed WWP1 gene dosage and expression level as well as WWP1's function. A copy number gain of WWP1 was found in 51% (18/35) of breast cancer cell lines and in 41% (17/41) of primary breast tumors. Expression of WWP1 mRNA was analyzed with real-time RT-PCR, Northern blot, and Western blot. WWP1 mRNA is up-regulated in 58% (19/33) of breast cancer cell lines, and overexpression of WWP1 is significantly correlated with a gene copy number gain. In a panel of cDNA from primary breast tumors and normal tissues, expression of WWP1 in tumors is significantly higher than that in normal tissues. Functionally, RNAi-mediated WWP1 knockdown significantly induced cell growth arrest and apoptosis in the MCF7 and HCC1500 breast cancer cell lines. Consistently, WWP1 inhibition activated caspases. Forced overexpression of WWP1 by the lentiviral system in 2 immortalized breast epithelial cell lines MCF10A and 184B5 promoted cell proliferation. These results suggest that genomic aberrations of WWP1 may contribute to the pathogenesis of breast cancer. 相似文献
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MicroRNAs and cancer 总被引:12,自引:0,他引:12
McManus MT 《Seminars in cancer biology》2003,13(4):253-258
The general basis of cancer is the loss of cell identity and inappropriate proliferation of cells. Classically, a universal paradigm in oncogenesis is the accumulation of mutations in the open reading frames of protein-encoding oncogenes and tumor suppressors. The identification of new classes of noncoding RNAs (ncRNA) important for development and cell homeostasis will likely change this current paradigm. Recent data suggests that a special class of ncRNAs called microRNAs might be involved in human disease. This review proposes a role for microRNAs in oncogenesis. 相似文献
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Libo Xiao Zhiping Wu Rui Feng Qishun Zhu Chenwei Gao Yan Chen Chun Hou Yonggui Wu 《中德临床肿瘤学杂志》2010,9(9):547-554
MicroRNAs (miRNAs) belong to a class of noncoding, regulatory RNAs that are involved in oncogenesis and show remarkable tissue
specificity. miRNAs are approximately 22 nt non-coding RNAs, which regulate gene expression in a sequence-specific manner
via translational inhibition or messenger RNA (mRNA) degradation, thus affecting various cellular processes. Since the discovery
of their fundamental mechanisms of action, the field of miRNAs has opened a new era in the understanding of small noncoding
RNAs. Recent evidence has shown that miRNA controls cell growth, apoptosis, and differentiation. Cancer is a complex genetic
disease caused by abnormalities in gene structure and expression, moreover, miRNA expression correlates with cancers and could
have a crucial function in tumor progression. Bioinformatic data indicate that each miRNA can control hundreds of target genes,
but identification of the accurate miRNA targets will be crucial to exploit the emerging knowledge of miRNA contribution to
cancer process. 相似文献
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Hannafon BN Sebastiani P de las Morenas A Lu J Rosenberg CL 《Breast cancer research : BCR》2011,13(2):R24
Introduction
microRNA (miRNA) are short, noncoding RNA that negatively regulate gene expression and may play a causal role in invasive breast cancer. Since many genetic aberrations of invasive disease are detectable in early stages, we hypothesized that miRNA expression dysregulation and the predicted changes in gene expression might also be found in early breast neoplasias. 相似文献14.
Several epidemiological studies on ataxia-telangiectasia families indicate that obligate ATM heterozygotes display an elevated risk for developing breast cancer. However, a molecular basis for a potential link between diminished ATM function and sporadic breast malignancy remains elusive. Here, we show that 78% (18 out of a panel of 23) of surgically removed breast tumors (stage II or greater) displayed aberrant methylation of the ATM proximal promoter region as judged by methylation-specific PCR. Aberrant methylation of the ATM promoter was independently confirmed in several tumors by bisulfite sequencing. Moreover, bisulfite sequencing indicated that this region of the genome is subject to dense methylation. Further, we found a highly significant correlation (P = 0.0006) between reduced ATM mRNA abundance, as measured by real-time RT-PCR, and aberrant methylation of the ATM gene promoter. These findings indicate that epigenetic silencing of ATM expression occurs in locally advanced breast tumors, and establish a link at the molecular level between reduced ATM function and sporadic breast malignancy. 相似文献
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Aydogdu E Katchy A Tsouko E Lin CY Haldosén LA Helguero L Williams C 《Carcinogenesis》2012,33(8):1502-1511
MicroRNAs (miRNAs) play pivotal roles in stem cell biology, differentiation and oncogenesis and are of high interest as potential breast cancer therapeutics. However, their expression and function during normal mammary differentiation and in breast cancer remain to be elucidated. In order to identify which miRNAs are involved in mammary differentiation, we thoroughly investigated miRNA expression during functional differentiation of undifferentiated, stem cell-like, murine mammary cells using two different large-scale approaches followed by qPCR. Significant changes in expression of 21 miRNAs were observed in repeated rounds of mammary cell differentiation. The majority, including the miR-200 family and known tumor suppressor miRNAs, was upregulated during differentiation. Only four miRNAs, including oncomiR miR-17, were downregulated. Pathway analysis indicated complex interactions between regulated miRNA clusters and major pathways involved in differentiation, proliferation and stem cell maintenance. Comparisons with human breast cancer tumors showed the gene profile from the undifferentiated, stem-like stage clustered with that of poor-prognosis breast cancer. A common nominator in these groups was the E2F pathway, which was overrepresented among genes targeted by the differentiation-induced miRNAs. A subset of miRNAs could further discriminate between human non-cancer and breast cancer cell lines, and miR-200a/miR-200b, miR-146b and miR-148a were specifically downregulated in triple-negative breast cancer cells. We show that miR-200a/miR-200b can inhibit epithelial-mesenchymal transition (EMT)-characteristic morphological changes in undifferentiated, non-tumorigenic mammary cells. Our studies propose EphA2 as a novel and important target gene for miR-200a. In conclusion, we present evidentiary data on how miRNAs are involved in mammary cell differentiation and indicate their related roles in breast cancer. 相似文献
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Baig RM Mahjabeen I Sabir M Masood N Hafeez S Malik FA Kayani MA 《Asian Pacific journal of cancer prevention》2011,12(10):2773-2778
The PTEN gene, a candidate tumor suppressor, is one of the more commonly inactivated and extensively studied genes in cancer. However, few data are available about the role of germ line mutations of this gene in sporadic breast cancer cases. The purpose of this study was to determine extent of involvement of this gene in breast cancer in Pakistan. To test the hypothesis that genetic variations of PTEN play a role in the etiology of breast cancer, a population based case-control study was conducted in 350 breast cancer patients along 400 healthy controls. After extracting DNA from blood, the whole coding sequence of PTEN along with intron/exon boundaries was genotyped by polymerase chain reaction-single stranded conformational polymorphism. Sequencing analysis revealed nineteen different types of mutations in different regions of PTEN (in exon 2, 4, 5, 6, 7 and splicing sites of intron 2 and 4 and also in the 3' UTR region), including 3 silent, 8 missense, 2 frame shift and 6 splice site variations. Among the observed variations in this study, three missense mutations have already been reported i.e. 319G>A (Asp106Asn), 389G>A (Arg129Gln) and 482G>A (Arg160Lys) in different populations. The present results suggest that a wide range of germline PTEN mutations may play a role in the pathogenesis of breast cancer. 相似文献
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目的:探讨结肠癌转移相关基因1(metastasis-associated in colon cancer 1,MACC1)及其靶蛋白SPON2在乳腺癌组织中的表达及与临床病理因素的相关性,并评估它们对乳腺癌患者预后的影响。方法:收集2011年1月至2011年12月间于同济医院行乳腺癌根治术的126例乳腺癌患者的癌和相应癌旁组织石蜡标本,应用免疫组化Envision法检测MACC1和SPON2蛋白在癌及癌旁组织中的表达,分析MACC1和SPON2表达与乳腺癌临床病理特征及患者预后的关系。结果:MACC1主要定位于细胞质及细胞膜,SPON2在细胞膜、细胞质及细胞外基质中出现表达,MACC1和SPON2蛋白在乳腺癌组织中的表达均明显高于癌旁组织(68.3% vs 21.4%和71.4% vs 17.5%,P均<0.01)。MACC1表达与乳腺癌患者组织学分级、TNM 分期、淋巴结转移、肿瘤复发显著相关(P均<0.05);SPON2表达与患者TNM分期、淋巴结转移、Nottingham预后指数、肿瘤复发显著相关(P均<0.05);二者均与ER、PR及HER2状态无关(P>0.05),且乳腺癌组织中MACC1和SPON2的表达呈显著正相关(P<0.001)。Kaplan-Meier生存曲线显示,MACC1和SPON2高表达的患者总生存期(OS)和无进展生存期(PFS)均较短(P均<0.001);Cox比例风险模型分析表明,MACC1和SPON2过表达是乳腺癌患者预后的独立影响因素(P均<0.001)。结论:MACC1和SPON2可能参与了乳腺癌的发生、发展,在乳腺癌预后评估中具有一定价值,可能成为潜在的靶点为乳腺癌治疗提供一些新的思路。 相似文献
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Cancer of the esophagus is a highly aggressive disease associated with an overall poor prognosis. There is an insistent need for improving our understanding of the molecular basis of this disease. The recent emergence of observations on the role of microRNAs in cancer and their potential as biomarkers has prompted many investigations to examine their relevance to esophageal cancer. This article provides an introduction to microRNA biology and the techniques involved in studying them, and summates what is now known about their role and utility in regard to neoplastic esophageal diseases. 相似文献
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