Tumor metastasis is the main cause of death in patients with solid tumors. The epithelial-mesenchymal transition(EMT) process, in which epithelial cells are converted into mesenchymal cells, is frequently activated du...Tumor metastasis is the main cause of death in patients with solid tumors. The epithelial-mesenchymal transition(EMT) process, in which epithelial cells are converted into mesenchymal cells, is frequently activated during cancer invasion and metastasis. MicroRNAs(miRNAs) are small, non-coding RNAs that provide widespread expressional control by repressing mRNA translation and inducing mRNA degradation. The fundamental roles of miRNAs in tumor growth and metastasis have been increasingly well recognized. A growing number of miRNAs are reported to regulate tumor invasion/metastasis through EMT-related and/or non-EMT–related mechanisms. In this review, we discuss the functional role and molecular mechanism of miRNAs in regulating cancer metastasis and EMT.展开更多
【目的】通过对东方蜜蜂微孢子虫(Nosema ceranae)纯化孢子与侵染意大利蜜蜂(Apis mellifera ligustica,简称意蜂)工蜂的东方蜜蜂微孢子虫的差异表达miRNA(DEmiRNA)及其靶mRNA进行系统分析,筛选、分析和探讨病原毒力因子和侵染因子相关...【目的】通过对东方蜜蜂微孢子虫(Nosema ceranae)纯化孢子与侵染意大利蜜蜂(Apis mellifera ligustica,简称意蜂)工蜂的东方蜜蜂微孢子虫的差异表达miRNA(DEmiRNA)及其靶mRNA进行系统分析,筛选、分析和探讨病原毒力因子和侵染因子相关的DEmiRNA及调控网络,在miRNA组学层面揭示东方蜜蜂微孢子虫对意蜂的侵染机制。【方法】利用small RNA-seq(sRNA-seq)技术对东方蜜蜂微孢子虫感染7 d和10 d的意蜂工蜂中肠和东方蜜蜂微孢子虫纯化孢子(NcCK)进行深度测序,通过连续比对rRNA数据库、西方蜜蜂(Apis mellifera)基因组和东方蜜蜂微孢子虫基因组筛滤出处于侵染过程的东方蜜蜂微孢子虫(NcT1和NcT2)数据和东方蜜蜂微孢子虫孢子的测序数据。根据P≤0.05,|log2 fold change|≥1的标准,通过比较分析筛选出各比较组中的差异表达miRNA(differentially expressed miRNA,DEmiRNA)。通过相关生物信息学软件对DEmiRNA进行表达谱分析,靶mRNA预测及功能和代谢通路注释,以及调控网络的构建与分析。通过Stem-loop RT-qPCR验证DEmiRNA的差异表达趋势及测序数据的可靠性。【结果】NcCK vs NcT1、NcCK vs NcT2和NcT1 vs NcT2比较组分别包含164、122和60个DEmiRNA。Venn分析结果显示,3个比较组共有的上调和下调miRNA分别为5和6个。上述DEmiRNA分别预测出1885、1733和1524个靶mRNA。这些靶mRNA分别注释到27、25和26个功能条目,其中注释数量最多的是新陈代谢进程、催化活性、细胞进程、结合和细胞。上述靶mRNA可分别注释到84、84和84条代谢通路,其中注释数量最多的是代谢途径、核糖体和次级代谢产物生物合成。此外,对于NcCK vs NcT1、NcCK vs NcT2和NcT1 vs NcT2中的DEmiRNA,分别有35、26和12个靶向结合MAPK信号通路相关靶mRNA,分别有49、40和17个DEmiRNA靶向结合糖酵解/糖异生通路相关靶mRNA。进一步分析发现,东方蜜蜂微孢子虫的DEmiRNA参与调控蓖麻毒素B凝集素展开更多
Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition(EMT), during which cells dedifferentiate from a relative...Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition(EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas(TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This "paradox" can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating m RNA and micro RNA(mi RNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major mi RNAs and 214 m RNAs. Among the 8 mi RNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 mi RNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.展开更多
文摘Tumor metastasis is the main cause of death in patients with solid tumors. The epithelial-mesenchymal transition(EMT) process, in which epithelial cells are converted into mesenchymal cells, is frequently activated during cancer invasion and metastasis. MicroRNAs(miRNAs) are small, non-coding RNAs that provide widespread expressional control by repressing mRNA translation and inducing mRNA degradation. The fundamental roles of miRNAs in tumor growth and metastasis have been increasingly well recognized. A growing number of miRNAs are reported to regulate tumor invasion/metastasis through EMT-related and/or non-EMT–related mechanisms. In this review, we discuss the functional role and molecular mechanism of miRNAs in regulating cancer metastasis and EMT.
文摘【目的】通过对东方蜜蜂微孢子虫(Nosema ceranae)纯化孢子与侵染意大利蜜蜂(Apis mellifera ligustica,简称意蜂)工蜂的东方蜜蜂微孢子虫的差异表达miRNA(DEmiRNA)及其靶mRNA进行系统分析,筛选、分析和探讨病原毒力因子和侵染因子相关的DEmiRNA及调控网络,在miRNA组学层面揭示东方蜜蜂微孢子虫对意蜂的侵染机制。【方法】利用small RNA-seq(sRNA-seq)技术对东方蜜蜂微孢子虫感染7 d和10 d的意蜂工蜂中肠和东方蜜蜂微孢子虫纯化孢子(NcCK)进行深度测序,通过连续比对rRNA数据库、西方蜜蜂(Apis mellifera)基因组和东方蜜蜂微孢子虫基因组筛滤出处于侵染过程的东方蜜蜂微孢子虫(NcT1和NcT2)数据和东方蜜蜂微孢子虫孢子的测序数据。根据P≤0.05,|log2 fold change|≥1的标准,通过比较分析筛选出各比较组中的差异表达miRNA(differentially expressed miRNA,DEmiRNA)。通过相关生物信息学软件对DEmiRNA进行表达谱分析,靶mRNA预测及功能和代谢通路注释,以及调控网络的构建与分析。通过Stem-loop RT-qPCR验证DEmiRNA的差异表达趋势及测序数据的可靠性。【结果】NcCK vs NcT1、NcCK vs NcT2和NcT1 vs NcT2比较组分别包含164、122和60个DEmiRNA。Venn分析结果显示,3个比较组共有的上调和下调miRNA分别为5和6个。上述DEmiRNA分别预测出1885、1733和1524个靶mRNA。这些靶mRNA分别注释到27、25和26个功能条目,其中注释数量最多的是新陈代谢进程、催化活性、细胞进程、结合和细胞。上述靶mRNA可分别注释到84、84和84条代谢通路,其中注释数量最多的是代谢途径、核糖体和次级代谢产物生物合成。此外,对于NcCK vs NcT1、NcCK vs NcT2和NcT1 vs NcT2中的DEmiRNA,分别有35、26和12个靶向结合MAPK信号通路相关靶mRNA,分别有49、40和17个DEmiRNA靶向结合糖酵解/糖异生通路相关靶mRNA。进一步分析发现,东方蜜蜂微孢子虫的DEmiRNA参与调控蓖麻毒素B凝集素
基金supported by the U.S. National Institutes of Health grants (U24 CA143835 to IS and WZ, P50 CA083639 and P50 CA098258 to AKS)MD Anderson support grant (CA016672) to WZ+6 种基金a grant from the Blanton-Davis Ovarian Cancer Research Program to WZgrants from the Program for Changjiang Scholars, Innovative Research Team in University (PCSIRT) in Chinathe National Key Scientifi c and Technological Project (2011ZX0 9307-001-04)Tianjin Science and Technology Committee Foundation (09ZCZDSF04700) to KCa grant from National Nature Science Foundation of China (#81201651) to YSa grant from Fondazione CARIPLO (2013-0865) to DMthe A. Lavoy Moore Endowment Fund to YS and DY
文摘Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition(EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas(TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This "paradox" can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating m RNA and micro RNA(mi RNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major mi RNAs and 214 m RNAs. Among the 8 mi RNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 mi RNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.
