Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The molecular changes that have occurred in breast cancer cells through the introduction of the MZF-1 fragment

ABSTRACT: We used microarray gene expression analyses to search for epithelial-mesenchymal transition (EMT)-related genes that exhibited the greatest differences in expression in the MZF-1 fragment vector-transfected cells relative to the empty vector-transfected cells. Of the 22,203 genes analyzed in both cell lines, 1209 genes had a two-fold increase and 1557 genes had a two-fold decrease in Hs578T-M(S3) cells (P<0.05), and 1272 genes increased and 1494 genes decreased by a similar amount in MDA-MB-231-M(V4) cells. Combined, 821 of the same genes from both cell lines were up-regulated, and 931 of the same genes from both cell lines were down-regulated. The biological functions of these affected genes were diverse and included 11 EMT-related genes (ITGA5, SERPINE1 GNGI1, SEAP1, TIMP1, FN1, TMEFF1, SNAI2, VIM, CALD1 and MSN) which were down-regulated, and 5 MET-related genes (CDH1, TSPAN13, OCLN, KRT19 and DSP) which were up-regulated. To understand functions of MZF-1/Elk-1 heterodimers, we transfected the binding site-derived peptide to the cells to interrupt heterodimer formation, their DNA binding activity, PKCÎ± expression, cell migration and tumorigenicity were decreased, and the mesenchymal-epithelial transition (MET) was present.

ORGANISM(S): Homo sapiens

SUBMITTER: Jer-Yuh Liu

PROVIDER: E-GEOD-56306 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Project description:In this study we performed a systematic evaluation of functional miRNA-mRNA interactions associated with the aggressiveness of breast cancer cells using a combination of integrated miRNA and mRNA expression profiling, bioinformatics prediction, and functional assays. Analysis of the miRNA expression identified 11 miRNAs that were differentially expressed, including 7 down-regulated (miR-200c, miR-205, miR-203, miR-141, miR-34a, miR-183, and miR-375) and 4 up-regulated miRNAs (miR-146a, miR-138, miR-125b1 and miR-100), in aggressive cell lines when compared to normal and less aggressive cell lines. Transient overexpression of miR-200c, miR-205, and miR-375 in MDA-MB-231 cells led to the inhibition of cell migration and invasion. The integrated analysis of miRNA and mRNA expression identified 35 known and novel target genes of miR-200c, miR-205, and mir-375, including CFL2, LAMC1, TIMP2, ZEB1, CDH11, PRKCA, PTPRJ, PTPRM, LDHB, and SEC23A. Surprisingly, the majority of these genes (27 genes) were target genes of miR-200c, suggesting that it plays a more important role in regulating the aggressiveness of breast cancer cells. We characterized one of the target genes of miR-200c, CFL2, and demonstrated that CFL2 is overexpressed in aggressive breast cancer cell lines and can be significantly down-regulated by exogenous miR-200c. Tissue microarray analysis further revealed that CFL2 expression in primary breast cancer tissue correlated with tumor grade. To our knowledge, this study is the first systematic screening of functional miRNA target genes in aggressive breast cancer cells. The results obtained from this study may improve our understanding of the role of these candidate miRNAs and their target genes in relation to breast cancer aggressiveness and ultimately lead to the identification of novel biomarkers associated with prognosis. Affymetrix U133 plus arrays were performed according to the manufacturer's directions on RNA extracted from 12 breast cancer cell lines including 4 aggressive cell lines, 6 less aggressive cell lines and 2 imortalized breast epithelium cell lines

Project description:In this study we performed a systematic evaluation of functional miRNA-mRNA interactions associated with the aggressiveness of breast cancer cells using a combination of integrated miRNA and mRNA expression profiling, bioinformatics prediction, and functional assays. Analysis of the miRNA expression identified 11 miRNAs that were differentially expressed, including 7 down-regulated (miR-200c, miR-205, miR-203, miR-141, miR-34a, miR-183, and miR-375) and 4 up-regulated miRNAs (miR-146a, miR-138, miR-125b1 and miR-100), in aggressive cell lines when compared to normal and less aggressive cell lines. Transient overexpression of miR-200c, miR-205, and miR-375 in MDA-MB-231 cells led to the inhibition of cell migration and invasion. The integrated analysis of miRNA and mRNA expression identified 35 known and novel target genes of miR-200c, miR-205, and mir-375, including CFL2, LAMC1, TIMP2, ZEB1, CDH11, PRKCA, PTPRJ, PTPRM, LDHB, and SEC23A. Surprisingly, the majority of these genes (27 genes) were target genes of miR-200c, suggesting that it plays a more important role in regulating the aggressiveness of breast cancer cells. We characterized one of the target genes of miR-200c, CFL2, and demonstrated that CFL2 is overexpressed in aggressive breast cancer cell lines and can be significantly down-regulated by exogenous miR-200c. Tissue microarray analysis further revealed that CFL2 expression in primary breast cancer tissue correlated with tumor grade. To our knowledge, this study is the first systematic screening of functional miRNA target genes in aggressive breast cancer cells. The results obtained from this study may improve our understanding of the role of these candidate miRNAs and their target genes in relation to breast cancer aggressiveness and ultimately lead to the identification of novel biomarkers associated with prognosis. Affymetrix miRNA 1.0 arrays were performed according to the manufacturer's directions on small RNA extracted from 12 breast cancer cell lines including 4 aggressive cell lines, 6 less aggressive cell lines and 2 imortalized breast epithelium cell lines

Project description:Decoding post-transcriptional regulatory programs underlying gene expression is a crucial step toward a predictive dynamical understanding of cellular state transitions. Despite recent systematic efforts, the sequence determinants of such mechanisms remain largely uncharacterized. An important obstacle in revealing these elements stems from the contribution of local secondary structures in defining interaction partners in a variety of regulatory contexts, including but not limited to transcript stability, alternative splicing and localization. There are many documented instances where the presence of a structural regulatory element dictates alternative splicing patterns (e.g. human cardiac troponin T) or affects other aspects of RNA biology. Thus, a full characterization of post-transcriptional regulatory programs requires capturing information provided by both local secondary structures and the underlying sequence. We have developed a computational framework based on context-free grammars and mutual information that systematically explores the immense space of structural elements and reveals motifs that are significantly informative of genome-wide measurements of RNA behavior. The application of this framework to genome-wide mammalian mRNA stability data revealed eight highly significant elements with substantial structural information, for the strongest of which we showed a major role in global mRNA regulation. Through biochemistry, mass-spectrometry, and in vivo binding studies, we identified HNRPA2B1 as the key regulator that binds this element and stabilizes a large number of its target genes. Ultimately, we created a global post-transcriptional regulatory map based on the identity of the discovered linear and structural cis-regulatory elements, their regulatory interactions and their target pathways. This approach can also be employed to reveal the structural elements that modulate other aspects of RNA behavior. This SuperSeries is composed of the following subset Series: GSE35749: sRSM1 synthetic decoy vs. scrambled transfections in MDA-MB-231 cells GSE35753: HNRPA2B1 RIP-chip GSE35756: Whole-genome decay rate measurements in MDA-MB-231 cells transfected with HNRPA2B1 siRNAs versus controls GSE35757: siRNA-mediated HNRPA2B1 knock-down in MDA-MB-231 cells GSE35799: HNRPA2B1 HITS-CLIP Refer to individual Series