MicroRNA expression signature in gastric cancer

Objective: To identify the miRNA specific signature as novel diagnostic and prognostic tools for gastric cancer. Methods: miRNAs expression profiling of 3 normal gastric tissues, 24 malignant tissues, gastric cancer cell SGC7901 and normal gastric cell GES-1 were detected using microarray technology. The hierarchical clustering algorithm of the Cluster software was used to analyse the miRNAs expression of all samples. The expression levels of miR-433 and miR-9 which were significantly down-regulated in gastric cancer tissues and SGC7901 cells by microarray technology were validated by quantitative Real-time PCR (qRT-PCR).Results: Differential expressions of 26 individual miRNAs between normal samples (including 3 normal gastric tissues and GES-1 cells) and carcinomas (including 24 malignant tissues and SGC7901 cells) were discovered,19 of them showing down-regulation and 7 up-regulation in carcinoma samples. Hierarchical clustering of the cancer samples by their miRNA expression accurately separated the carcinomas from normal samples and further their histotypes of carcinomas. The expression levels of miR-433 and miR-9 were significantly down-regulated in gastric cancer tissues and SGC7901cells Conclusion: The differential expression of miR-433 and miR-9 may be used as a novel diagnostic tool for gastric cancer.     

MicroRNA expression profiling in human Barrett's carcinogenesis

Barrett's esophagus (BE) is characterized by the native stratified squamous epithelium (N) lining the esophagus being replaced by a columnar epithelium with intestinal differentiation (Barrett's mucosa; BM). BM is considered as the main risk factor for esophageal adenocarcinoma (Barrett's adenocarcinoma; BAc). MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting messenger RNAs and they are reportedly dysregulated in BM. To test the hypothesis that a specific miRNA expression signature characterizes BM development and progression, we performed miRNA microarray analysis comparing native esophageal mucosa with all the phenotypic lesions seen in the Barrett's carcinogenic process. Specimens were collected from 14 BE patients who had undergone esophagectomy, including: 14 with N, 14 with BM, 7 with low-grade intraepithelial neoplasia, 5 with high-grade intra-epithelial neoplasia and 11 with BAc. Microarray findings were further validated by quantitive real-time polymerase chain reaction and in situ hybridization analyses using a different series of consecutive cases (162 biopsy samples and 5 esophagectomies) of histologically proven, long-segment BE. We identified a miRNA signature of Barrett's carcinogenesis consisting of an increased expression of 6 miRNAs and a reduced expression of 7 miRNAs. To further support these results, we investigated target gene expression using the Oncomine database and/or immunohistochemical analysis. We found that target gene expression correlated significantly with miRNA dysregulation. Specific miRNAs are directly involved in BE progression to cancer. miRNA profiling significantly expands current knowledge on the molecular history of Barrett's carcinogenesis, also identifying molecular markers of cancer progression.     

MicroRNA gene expression deregulation in human breast cancer

MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. Indeed, miRNA aberrant expression has been previously found in human chronic lymphocytic leukemias, where miRNA signatures were associated with specific clinicobiological features. Here, we show that, compared with normal breast tissue, miRNAs are also aberrantly expressed in human breast cancer. The overall miRNA expression could clearly separate normal versus cancer tissues, with the most significantly deregulated miRNAs being mir-125b, mir-145, mir-21, and mir-155. Results were confirmed by microarray and Northern blot analyses. We could identify miRNAs whose expression was correlated with specific breast cancer biopathologic features, such as estrogen and progesterone receptor expression, tumor stage, vascular invasion, or proliferation index.     

MicroRNA expression patterns in the malignant progression of gliomas and a 5-microRNA signature for prognosis

MicroRNAs (miRNAs) are directly involved in the progression in various cancers. To date, no systematic researches have been performed on the expression pattern of miRNA during progression from low grade gliomas to anaplastic gliomas or secondary glioblastomas and those prognostic miRNAs in anaplastic gliomas and secondary glioblastomas. In the present study, high-throughput microarrays were used to measure miRNA expression levels in 116 samples in the different progression stages of glioma. We found that miRNA expression pattern totally altered when low grade gliomas progressed to anaplastic gliomas or secondary glioblastomas. However, anaplastic gliomas and secondary glioblastomas have similar expression pattern in miRNA level. Furthermore, we developed a five-miRNA signature (two protective miRNAs-miR-767-5p, miR-105; three risky miRNAs: miR-584, miR-296-5p and miR-196a) that could identify patients with a high risk of unfavorable outcome in anaplastic gliomas regardless of histology type. It should be highlighted that the five-miRNA signature can also identify patients who had a high risk of unfavorable outcome in secondary and TCGA Proneural glioblastomas, but not Neural, Classical and Mesenchymal glioblastomas. Taken together, our results demonstrate that miRNA expression patterns in the malignant progression of gliomas and a novel prognostic classifier, the five-miRNA signature, serve as a prognostic marker for patient risk stratification in anaplastic gliomas, Secondary and Proneural glioblastomas.     

MicroRNA signature predicts survival and relapse in lung cancer

We investigated whether microRNA expression profiles can predict clinical outcome of NSCLC patients. Using real-time RT-PCR, we obtained microRNA expressions in 112 NSCLC patients, which were divided into the training and testing sets. Using Cox regression and risk-score analysis, we identified a five-microRNA signature for the prediction of treatment outcome of NSCLC in the training set. This microRNA signature was validated by the testing set and an independent cohort. Patients with high-risk scores in their microRNA signatures had poor overall and disease-free survivals compared to the low-risk-score patients. This microRNA signature is an independent predictor of the cancer relapse and survival of NSCLC patients.     

肺癌缺氧A549细胞的microRNA芯片表达谱分析

目的:研究缺氧对肺腺癌A549细胞中microRNA表达谱的影响,分析靶基因参与的生物学功能和通路。方法:基于miRNA芯片技术和生物信息学分析方法,分析缺氧条件和正常氧条件下培养的A549细胞中差异表达的miRNA,并预测这些miRNA的靶基因,分析靶基因参与的生物学功能和通路。结果:本研究共筛选出14个差异表达miRNA,包括9个在缺氧细胞中上调miRNA和5个下调miRNA。上调和下调miRNA的靶基因都参与DNA转录、核染色质修饰等功能,并且都参与Wnt信号、TGF-β信号和MAPK信号通路。结论:缺氧的肺腺癌A549细胞中miRNA表达谱发生了显著改变,差异表达miRNA对某些基因具有调控作用。     

肺腺癌患者淋巴转移的分子指纹鉴定

背景与目的：远处转移是肺癌患者的重要死因,癌转移可能与细胞内基因表达模式改变有关。急需运用新技术来筛选和分析这些基因,以便进一步阐明癌转移的机制并寻找新的治疗靶点。本研究旨在筛选肺腺癌患者淋巴转移差异表达基因。方法：原发癌组织及区域淋巴结取自22例接受根治性手术的肺腺癌患者。根据组织来源将标本分为三组：不伴淋巴转移的肺腺癌组织（TxN-,n=11）、伴有淋巴转移的肺腺癌组织（TxN＋,n=11）及相应转移淋巴结中的肺腺癌细胞（N＋,n=11）。对各组进行激光显微切割以获得纯净癌细胞,T7RNA线性扩增获取足够量的RNA,实验通道和参照通道分别标记以后与含6000个已知人类基因或表达序列标签的cDNA基因芯片杂交,扫描荧光信号以后进行数据分析。结果：TxN＋组与TxN-组共有17个差异表达基因,其中12个基因表达上调,5个基因表达下调。有53个基因可将N＋组与TxN＋组区分开,其中在N＋组高表达的基因有25个,在TxN＋组高表达的有28个。结论：早期癌形成中的遗传学变化和后期癌进展中的获得性分子学变异共同决定肺腺癌的淋巴转移。     

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。     

DNA methylation regulates MicroRNA expression

MicroRNAs (miRNAs), an important class of small regulatory molecules for gene expression, are transcribed by RNA polymerase II. But little is known about the mechanisms that control miRNA expression. Comparing miRNA expression profiles between colon cancer cell line HCT 116 and its derivative, DNA methyltransferase 1 and 3b (DNMT1 and DNMT3b) double knockout cell line, we found that the expression of about 10% miRNAs was regulated by DNA methylation. In addition, neither 5-aza-2'-deoxycytidine treatment nor deletion of DNMT1 alone recapitulated miRNA expression profile seen in the double knockout cell line, suggesting that miRNA expression was tightly controlled by DNA methylation and partial methylation reduction was not sufficient for miRNA reexpression. We also found that HOXA3 and HOXD10 were putative targets of mir-10a, one of the differentially expressed miRNAs that is located in HOX gene cluster.     

A gene expression signature associated with metastatic outcome in human leiomyosarcomas

Metastasis is a major factor associated with poor prognosis in cancer, but little is known of its molecular mechanisms. Although the clinical behavior of soft tissue sarcomas is highly variable, few reliable determinants of outcome have been identified. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Here, we have chosen leiomyosarcoma as a model for examining the relationship between gene expression profile and the development of metastasis in soft tissue sarcomas. Using cDNA microarray, we have identified a gene expression signature associated with metastasis in sarcoma that allowed prediction of the future development of metastases of primary tumors (Kaplan-Meier analysis P = 0.001). Our finding may aid the tailoring of therapy for individual sarcoma patients, where the aggressiveness of treatment is affected by the predicted outcome of disease.     

Cyclooxygenase-2 expression in human soft-tissue sarcomas is related to epithelial differentation

BACKGROUND: Cyclooxygenase-2 (Cox-2) is expressed by several types of epithelial malignancies, i.e., carcinomas, and inhibition of Cox-2 may have a therapeutic role in chemoprevention and treatment of cancer. The role of Cox-2 in non-epithelial malignancies, however, is unclear. MATERIALS AND METHODS: We investigated, by immuno- histochemistry, the expression of Cox-2 in 103 human soft-tissue sarcomas. RESULTS: All 10 biphasic synovial sarcomas were positive for Cox-2, but positivity was observable only in the epithelial component of these tumours. Excluding sarcomas with epithelial differentation, uniform staining of the tumour was observed in only 2 samples. In addition, positivity for Cox-2 appeared in tumour cells in only 18 samples around necrotic areas. CONCLUSION: In human soft-tissue sarcomas, Cox-2 expression seems to be associated with epithelial differentation and, in some types of sarcomas, to be expressed in otherwise negative tumours at sites of necrosis.     

MicroRNA profiling in human medulloblastoma

Medulloblastoma is an aggressive brain malignancy with high incidence in childhood. Current treatment approaches have limited efficacy and severe side effects. Therefore, new risk-adapted therapeutic strategies based on molecular classification are required. MicroRNA expression analysis has emerged as a powerful tool to identify candidate molecules playing an important role in a large number of malignancies. However, no data are yet available on human primary medulloblastomas. A high throughput microRNA expression profiles was performed in human primary medulloblastoma specimens to investigate microRNA involvement in medulloblastoma carcinogenesis. We identified specific microRNA expression patterns which distinguish medulloblastoma differing in histotypes (anaplastic, classic and desmoplastic), in molecular features (ErbB2 or c-Myc overexpressing tumors) and in disease-risk stratification. MicroRNAs expression profile clearly differentiates medulloblastoma from either adult or fetal normal cerebellar tissues. Only a few microRNAs displayed upregulated expression, while most of them were downregulated in tumor samples, suggesting a tumor growth-inhibitory function. This property has been addressed for miR-9 and miR-125a, whose rescued expression promoted medulloblastoma cell growth arrest and apoptosis while targeting the proproliferative truncated TrkC isoform. In conclusion, misregulated microRNA expression profiles characterize human medulloblastomas, and may provide potential targets for novel therapeutic strategies.