Project description:Gene and miRNA profiles from a unique Chinese/Caucasian trans-ethnic collection of breast cancer from Shanghai (China) and Milan (Italy) were compared using an unsupervised approach that identified similar clusters of correlated features in Chinese and Caucasian datasets. Partition of gene expression data using previously published gene signatures, such as the PAM50 intrinsic gene list and the extracellular matrix (ECM) genes, revealed Chinese and Caucasian subgroups with equivalent gene and miRNA expression profiles. A significant reduction of Luminal-A tumors was observed in the Chinese series. Tissue samples from 78 Chinese (Han Chinese) and 97 Italian (South Europe Caucasian) consecutive primary breast tumors were subjected to gene and miRNA profiling. Tissue specimens, initially collected respectively in the Chinese and Italian hospitals, were all stored, randomly processed and analyzed in identical experimental conditions in the Italian center to minimize pre-analytical, instrumental and computational variability, enabling direct comparison of gene and miRNA profiles from the two groups.
Project description:Gene and miRNA profiles from a unique Chinese/Caucasian trans-ethnic collection of breast cancer from Shanghai (China) and Milan (Italy) were compared using an unsupervised approach that identified similar clusters of correlated features in Chinese and Caucasian datasets. Partition of gene expression data using previously published gene signatures, such as the PAM50 intrinsic gene list and the extracellular matrix (ECM) genes, revealed Chinese and Caucasian subgroups with equivalent gene and miRNA expression profiles. A significant reduction of Luminal-A tumors was observed in the Chinese series. Tissue samples from 78 Chinese (Han Chinese) and 97 Italian (South Europe Caucasian) consecutive primary breast tumors were subjected to gene and miRNA profiling. Tissue specimens, initially collected respectively in the Chinese and Italian hospitals, were all stored, randomly processed and analyzed in identical experimental conditions in the Italian center to minimize pre-analytical, instrumental and computational variability, enabling direct comparison of gene and miRNA profiles from the two groups.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes
Project description:MicroRNA (miRNA/miR) miR526b and miR655 overexpressed tumor cell-free secretions promote breast cancer phenotypes in the tumor microenvironment (TME). However, the mechanisms of miRNA regulating TME have never been investigated. With mass spectrometry analysis of MCF7-miRNA-overexpressed versus miRNA-low MCF7-Mock tumor cell secretomes, we identified 34 novel secretory proteins coded by eight genes YWHAB, TXNDC12, MYL6B, SFN, FN1, PSMB6, PRDX4, and PEA15 those are differentially regulated. We used bioinformatic tools and systems biology approaches to identify these markers’ role in breast cancer. Gene ontology analysis showed that the top functions are related to apoptosis, oxidative stress, membrane transport, and motility, supporting miRNA-induced phenotypes. These secretory markers expression is high in breast tumors, and a strong positive correlation exists between upregulated markers’ mRNA expressions with miRNA cluster expression in luminal A breast tumors. Gene expression of secretome markers is higher in tumor tissues compared to normal samples, and immunohistochemistry data supported gene expression data. Moreover, both up and downregulated marker expressions are associated with breast cancer patient survival. miRNA regulates these marker protein expressions by targeting transcription factors of these genes. Premature miRNA (pri-miR526b and pri-miR655) are established breast cancer blood biomarkers. Here we report novel secretory markers upregulated by miR526b and miR655 (YWHAB, MYL6B, PSMB6, and PEA15) are significantly upregulated in breast cancer patients’ plasma, and are potential breast cancer biomarkers.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.