The primary goal of this study is to identify molecular subtypes of breast cancer through gene expression profiles of 327 breast cancer samples and determine molecular and clinical characteristics of different breast cancer subtypes.
Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization.
Sex, Age, Specimen part
View SamplesHuman embryonic stem (hES) cells have the capacities to propagate for extended periods and to differentiate into cell types from all three germ layers both in vitro and in vivo. These characteristics of self-renewal and pluripotency enable hES cells having the potential to provide an unlimited supply of different cell types for tissue replacement, drug screening, and functional genomics studies. The hES-T3 cells with normal female karyotype cultured on either mouse embryonic fibroblasts (MEF) in hES medium (containing 4 ng/ml bFGF) (T3MF) or feeder-free Matrigel in MEF-conditioned medium (supplemented with additional 4 ng/ml bFGF) (T3CM) were found to express very similar profiles of mRNAs and microRNAs, indicating that the unlimited self-renewal and pluripotency of hES cells can be maintained by continuing culture on these two conditions. However, the expression profiles, especially microRNAs, of the hES-T3 cells cultured on Matrigel in hES medium supplemented with 4 ng/ml bFGF and 5 ng/ml activin A (T3BA) were found to be different from those of T3MF and T3CM cells. In T3BA cells, four hES cell-specific microRNAs miR-372, miR-302d, miR-367 and miR-200c, as well as three other microRNAs miR-199a, miR-19a and miR-217, were found to be up-regulated, whereas five miRNAs miR-19b, miR-221, miR-222, let-7b and let-7c were down-regulated by activin A. Thirteen abundantly differentially expressed mRNAs, including NR4A2, ERBB4, CXCR4, PCDH9, TMEFF2, CD24 and COX6A1 genes, targeted by seven over-expressed miRNAs were identified by inverse expression levels of these seven microRNAs to their target mRNAs in T3BA and T3CM cells. The NR4A2, ERBB4 and CXCR4 target genes were further found to be regulated by EGF and/or TNF. The 50 abundantly differentially expressed genes targeted by five under-expressed miRNAs were also identified. The abundantly expressed mRNAs in T3BA and T3CM cells were also analyzed for the network and signaling pathways, and roles of activin A in cell proliferation and differentiation were found. These findings will help elucidate the complex signaling network which maintains the self-renewal and pluripotency of hES cells.
Identification of microRNAs regulated by activin A in human embryonic stem cells.
Sex, Cell line
View SamplesTrans-splicing is a post-transcriptional event that joins exons from separate pre-mRNAs. Detection of trans-splicing is usually severely hampered by experimental artifacts and genetic rearrangements. Here, we develop a new computational pipeline, TSscan, which integrates different types of high-throughput long-/short-read transcriptome sequencing of different human embryonic stem cell (hESC) lines to effectively minimize false positives while detecting trans-splicing. Combining TSscan screening with multiple experimental validation steps revealed that most chimeric RNA products were platform-dependent experimental artifacts of RNA sequencing. We successfully identified and confirmed four trans-spliced RNAs, including the first reported trans-spliced large intergenic noncoding RNA ("tsRMST"). We showed that these trans-spliced RNAs were all highly expressed in human pluripotent stem cells and differentially expressed during hESC differentiation. Our results further indicated that tsRMST can contribute to pluripotency maintenance of hESCs by suppressing lineage-specific gene expression through the recruitment of NANOG and the PRC2 complex factor, SUZ12. Taken together, our findings provide important insights into the role of trans-splicing in pluripotency maintenance of hESCs and help to facilitate future studies into trans-splicing, opening up this important but understudied class of post-transcriptional events for comprehensive characterization
Integrative transcriptome sequencing identifies trans-splicing events with important roles in human embryonic stem cell pluripotency.
Specimen part
View SamplesThese paired HCC and non-tumorous liver tissues were used to determine highly dfferentially expressed genes in HCC and non-tumorous liver tissue.
Plasmalemmal Vesicle Associated Protein (PLVAP) as a therapeutic target for treatment of hepatocellular carcinoma.
Specimen part
View SamplesEpithelial Hedgehog (Hh) ligands regulate several aspects of fetal intestinal organogenesis and emerging data implicate the Hh pathway in inflammatory signaling in adult colon. We investigated the effects of chronic Hh inhibition in vivo and profiled molecular pathways acutely modulated by Hh signaling in the intestinal mesenchyme.
Hedgehog is an anti-inflammatory epithelial signal for the intestinal lamina propria.
Specimen part
View SamplesMicroRNAs (miRNAs) are noncoding RNAs of approximately 22 nucleotides in length that usually suppress the translation of target messenger RNAs (mRNAs) through partial complementarity to the 3 untranslated region (3 UTR) of protein-coding mRNAs in animals. However, there is increasing evidence that miRNAs can also reduce the steady-state levels of their target mRNAs in animals. In this investigation, both miRNA and mRNA profiles from the undifferentiated human embryonic stem cell line hES-T3 (T3ES), hES-T3 derived embryoid bodies (T3EB) and hES-T3 differentiated fibroblast-like cells (T3DF) were quantitatively determined. Three common target genes of three highly expressed hES cell-specific miRNAs were identified by inverse expression levels of miRNAs to their target mRNAs.
Target identification of microRNAs expressed highly in human embryonic stem cells.
Sex, Disease, Cell line
View SamplesTo investigate the regulation of TCF12 on downstream genes in OSCC, we performed GeneChip analysis using OECM1 expression cell subclones and HSC3 knockdown cell subclones.
MicroRNA-211 Enhances the Oncogenicity of Carcinogen-Induced Oral Carcinoma by Repressing TCF12 and Increasing Antioxidant Activity.
Specimen part, Cell line
View SamplesThe purpose of this study is to characterize gene expression changes that occur when conditional knock-out of Srf rescues mutant phenotypes in the cornea of Dstncorn1 mice.
Serum response factor: positive and negative regulation of an epithelial gene expression network in the destrin mutant cornea.
Specimen part
View SamplesType 1 diabetes is an autoimmune destruction of pancreatic islet beta cell disease, and it is important to find new alternative source of the islet beta cells to replace the damaged cells. Human embryonic stem (hES) cells possess unlimited self-renewal and pluripotency and thus have the potential to provide an unlimited supply of different cell types for tissue replacement. The hES-T3 cells with normal female karyotype were first differentiated into embryoid bodies and then induced to generate the pancreatic islet-like cell clusters, which expressed pancreatic islet cell-specific markers of insulin, glucagon and somatostatin. The expression profiles of microRNAs and mRNAs from the pancreatic islet-like cell clusters were further analyzed and compared with those of undifferentiated hES-T3 cells and differentiated embryoid bodies. MicroRNAs negatively regulate the expression of protein-coding mRNAs. The pancreatic islet-like cell clusters were found to exhibit very high expression of microRNAs miR-186, miR-199a and miR-339, which down-regulated the expression of LIN28, PRDM1, CALB1, GCNT2, RBM47, PLEKHH1, RBPMS2 and PAK6. Therefore, these microRNAs are very likely to play important regulatory roles in the differentiation of pancreatic islet cells and early embryonic development.
Identification of microRNAs expressed highly in pancreatic islet-like cell clusters differentiated from human embryonic stem cells.
Sex, Disease, Cell line
View SamplesRNAs were isolated from primary cultures after 24 hour treatment with IL-17A or IL-6 (10 ng/ml) in primary human TBE cells.
IL-17 markedly up-regulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kappaB signaling pathways.
Specimen part
View Samples