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The complex regulatory network between microRNAs and gene expression remains an unclear domain of active research. We proposed to address in part this complex regulation with a novel approach for the genome-wide identification of biomodules derived from paired microRNA and mRNA profiles, which could reveal correlations associated with a complex network of dys-regulation in human cancer. Two published expression datasets for 68 samples with 11 distinct types of epithelial cancers and 21 samples of normal tissues were used, containing microRNA expression and gene expression profiles, respectively. As results, the microRNA expression used jointly with mRNA expression can provide better classifiers of epithelial cancers against normal epithelial tissue than either dataset alone (P=1×10–10, F test). We identified a combination of 6 microRNA-mRNA biomodules that optimally classified epithelial cancers from normal epithelial tissue (total accuracy = 93.3%; 95% confidence intervals: 86%–97%), using penalized logistic regression (PLR) algorithm and three-fold cross-validation. Three of these biomodules are individually sufficient to cluster epithelial cancers from normal tissue using mutual information distance. The biomodules contain 10 distinct microRNAs and 98 distinct genes, including well known tumor markers such as miR-15a, miR-30e, IRAK1, TGFBR2, DUSP16, CDC25B and PDCD2. In addition, there is a significant enrichment (Fisher’s exact test P=3×10–10) between putative microRNA-target gene pairs reported in 5 microRNA target databases and the inversely correlated microRNA-mRNA pairs in the biomodules. Further, microRNAs and genes in the biomodules were found in abstracts mentioning epithelial cancers (Fisher’s Exact test, unadjusted P<0.05). Taken together, these results strongly suggest that the discovered microRNA-mRNA biomodules correspond to regulatory mechanisms common to human epithelial cancer samples. In conclusion, we developed and evaluated a novel comprehensive method to systematically identify, on a genome scale, microRNA-mRNA expression biomodules common to distinct cancers of the same tissue. These biomodules also comprise novel microRNA and genes as well as an imputed regulatory network, which may accelerate the work of cancer biologists as large regulatory maps of cancers can be drawn efficiently for hypothesis generation. 相似文献
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microRNA对肿瘤细胞增殖与分化的调控 总被引:1,自引:0,他引:1
microRNA(miRNA)是一种长度约为22核苷酸(nt)的非编码RNA,其主要通过碱基互补与靶mRNA的3'端非翻译区(3'UTR)结合,导致靶mRNA降解或抑制蛋白质的合成,在转录后水平调节基因的表达.miRNA突变、缺失或表达水平的异常会导致生理的异常与疾病的发生,与人类肿瘤疾病密切相关,它具有类似于癌基因或抑癌基因的作用,可参与肿瘤细胞的增殖、分化和细胞凋亡等调控过程.miRNA在肿瘤诊断和治疗方面具有广阔的应用前景. 相似文献
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YuXian Zhu 《科学通报(英文版)》2010,55(21):2198-2203
The biosynthesis and signaling of plant hormones play a critical role in almost all biological processes. It is well-documented that phytohormones cross-talk with each other. Epigenetic mechanisms were suggested to regulate expression of downstream targets in hormone signaling pathways that help implement hormone functions. This new layer of complexities that integrate epigenetic information such as DNA methylation, chromatin remodeling, histone modification, microRNAs and siRNAs with plant hormone signaling and regulations of gene expression, has been gradually revealed. In this short review, the author tries to assemble recent progress to establish a molecular linkage between these two large and momentum research fields and also to help readers digest the literature. 相似文献
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Zheng?Hu Yi?Tie GuiXiang?Lü HanJiang?Fu RuiYun?Xing Jie?Zhu ZhiXian?Sun XiaoFei?ZhengEmail author 《科学通报(英文版)》2013,58(36):4622-4629
An increasing data indicates that altered microRNAs (miRNAs) participate in the radiation-induced DNA damage response. However, a correlation of mRNA and miRNA profiles across the entire genome and in response to irradiation has not been thor- oughly assessed. We analyzed miRNA microarray data collected from HeLa cells after ionizing radiation (IR), quantified the ex- pression profiles of mRNAs and performed comparative analysis of the data sets using target prediction algorithms, Gene Ontol- ogy (GO) analysis, pathway analysis, and gene network construction. The results showed that the altered miRNAs were involved in regulation of various cellular functions, miRNA-gene network analyses revealed that miR- 186, miR- 106b, miR- 15 a/b, CCND 1 and CDK6 played vital role in the cellular radiation response. Using qRT-PCR, we confirmed that twenty-two miRNAs showed differential expression in HeLa cells treated with IR and some of these miRNAs affected cell cycle progression. This study demonstrated that miRNAs influence gene expression in the entire genome during the cellular radiation response and suggested vital pathways for further research. 相似文献