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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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MiRNA Signatures Associate with Pathogenesis and Progression of Osteosarcoma

ABSTRACT: In order to investigate the genes differentially expressed between osteosarcoma and their normal bone counterpart we carried out class comparisons algorithms in BRB-ArrayTools with the paired t test.The CEL files were imported and robust multi-array averaging normalized. Genes whose expression differed by at least 1.5-fold from the median in at least 20% of the arrays were used.

ORGANISM(S): Homo sapiens

SUBMITTER: Marco Galasso

PROVIDER: E-MEXP-3628 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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miRNA signatures associate with pathogenesis and progression of osteosarcoma.

Jones Kevin B KB Salah Zaidoun Z Del Mare Sara S Galasso Marco M Gaudio Eugenio E Nuovo Gerard J GJ Lovat Francesca F LeBlanc Kimberly K Palatini Jeff J Randall R Lor RL Volinia Stefano S Stein Gary S GS Croce Carlo M CM Lian Jane B JB Aqeilan Rami I RI

Cancer research 20120220 7

Osteosarcoma remains a leading cause of cancer death in adolescents. Treatment paradigms and survival rates have not improved in two decades. Driving the lack of therapeutic inroads, the molecular etiology of osteosarcoma remains elusive. MicroRNAs (miRNAs) have demonstrated far-reaching effects on the cellular biology of development and cancer. Their role in osteosarcomagenesis remains largely unexplored. Here we identify for the first time an miRNA signature reflecting the pathogenesis of oste ...[more]

PMID: 22350417

Similar Datasets

miRNA signatures associate with pathogenesis and progression of osteosarcoma.

Project description:Osteosarcoma remains a leading cause of cancer death in adolescents. Treatment paradigms and survival rates have not improved in two decades. Driving the lack of therapeutic inroads, the molecular etiology of osteosarcoma remains elusive. MicroRNAs (miRNAs) have demonstrated far-reaching effects on the cellular biology of development and cancer. Their role in osteosarcomagenesis remains largely unexplored. Here we identify for the first time an miRNA signature reflecting the pathogenesis of osteosarcoma from surgically procured samples from human patients. The signature includes high expression of miR-181a,miR-181b, and miR-181c as well as reduced expression of miR-16, miR-29b, and miR-142-5p. We also demonstrate that miR-181b and miR-29b exhibit restricted expression to distinct cell populations in the tumor tissue. Further, higher expression of miR-27a and miR-181c* in pre-treatment biopsy samples characterized patients who developed clinical metastatic disease. In addition, higher expression of miR-451 and miR-15b in pre-treatment samples correlated with subsequent positive response to chemotherapy. In vitro and in vivo functional validation in osteosarcoma cell lines confirmed the tumor suppressive role of miR-16 and the pro-metastatic role of miR-27a. Furthermore, predicted target genes for miR-16 and miR-27a were confirmed as down-regulated by real-time PCR. Affymetrix array profiling of cDNAs from the osteosarcoma specimens and controls were interrogated according to predicted targets of miR-16, miR142-5p, miR-29b, miR-181a/b, and miR-27a. This analysis revealed positive and negative correlations highlighting pathways of known importance to osteosarcoma, as well as novel genes. Thus, our findings establish a miRNA signature associated with pathogenesis of osteosarcoma as well as critical pre-treatment biomarkers of metastasis and responsiveness to therapy.

| S-EPMC3328547 | biostudies-literature

Comparative analysis of genome-wide DNA methylation identifies patterns that associate with conserved transcriptional programs in osteosarcoma

Project description:Osteosarcoma is an aggressive tumor of the bone that primarily affects young adults and adolescents. Osteosarcoma is characterized by genomic chaos and heterogeneity. While inactivation of tumor suppressor p53 TP53 is nearly universal other high frequency mutations or structural variations have not been identified. Despite this genomic heterogeneity, key conserved transcriptional programs associated with survival have been identified across human, canine and induced murine osteosarcoma. The epigenomic landscape, including DNA methylation, plays a key role in establishing transcriptional programs in all cell types. The role of epigenetic dysregulation has been studied in a variety of cancers but has yet to be explored at scale in osteosarcoma. Here we examined genome-wide DNA methylation patterns in 24 human and 44 canine osteosarcoma samples identifying groups of highly correlated DNA methylation marks in human and canine osteosarcoma samples. We also link specific DNA methylation patterns to key transcriptional programs in both human and canine osteosarcoma. Building on previous work, we built a DNA methylation-based measure for the presence and abundance of various immune cell types in osteosarcoma. Finally, we determined that the underlying state of the tumor, and not changes in cell composition, were the main driver of differences in DNA methylation across the human and canine samples. Significance: This is the first large scale study of DNA methylation in osteosarcoma and lays the ground work for the exploration of DNA methylation programs that help establish conserved transcriptional programs in the context of different genomic landscapes.

2020-05-01 | GSE149679 | GEO

Transcription profiling of the human K562 cell line treated with the polyamide-Chl conjugate 1R-Chl

Project description:To determine whether the polyamide-Chl conjugate 1R-Chl would cause similar changes in global gene expression in K562 cells, affymetrix gene chip analysis was performed using 1R-Chl. Through class comparison analysis, 1R-Chl affected the levels of transcription and genes of interest were determined. Experiment Overall Design: K562 cells were incubated with 1R-Chl (at 250 nM) or in the absence of polyamide, in triplicate for 24 h before RNA purification and microarray analysis at The Scripps Research Institute microarray facility. Affymetrix U133A Plus 2.0 GeneChips were hybridized in groups of three for each of the two groups. The Affymetrix probe set data were imported into BRB Arraytools (3.5.0 Beta 2), selecting the U133 chips used in the experiment and leaving all filters off.

2008-06-16 | E-GEOD-8832 | biostudies-arrayexpress

MicroRNA profiling by array of human osteosarcoma and their normal bone counterpart

Project description:Profiling array: in order to investigate the microRNAs differentially expressed between osteosarcoma and their normal bone counterpart. Specimens were kept at 4 C in RNAlater for up to 1 week, then stored at 80 C. When formal pathologic interpretation of histology from other portions of the biopsy specimen rendered a diagnosis of osteosarcoma, the RNA-preserving tissue specimens were banked and annotated. In preparation for these specific experiments, total RNA was extracted from banked specimens with the TRIzol reagent and method (Invitrogen). Control samples were derived from to-be-discarded bone fragments obtained from similarly consented patients undergoing debridement surgeries for acute, traumatic injuries to the long bones.

2012-05-21 | E-MTAB-1136 | biostudies-arrayexpress

Identification of a Potential Ovarian Cancer Stem Cell Gene Expression Profile from Advanced Stage Papillary Serous Ovarian Cancer

Project description:To identify the potential ovarian cancer stem cell gene expression profile from isolated side population of fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma Microarrays were used to interrogate the differentially expressed genes between side population (SP) and main population (MP) isolated from fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma, and the results were analyzed by paired T-test using BRB-ArrayTools

2011-11-23 | GSE33874 | GEO

Comparative genomic hybridization of human osteosarcoma cell lines

Project description:Comparative genomic hybridisation of 20 osteosarcoma cell lines using a homemade 1 Mb BAC/PAC microarray.

2010-02-10 | E-MEXP-1750 | biostudies-arrayexpress

Paget's associated osteosarcoma

Project description:Paget's associated osteosarcoma

| PRJNA343233 | ENA

The impact of calorie restriction and diet-induced obesity on microRNA expression

Project description:We analyzed the impact of calorie restriction and diet-induced obesity on expression of microRNAs in the mouse colon. For this analysis, data was LOESS normalized in R. Data was then imported into BRB Array for analysis. We identified microRNAs that were altered in response to calorie-restriction and diet-induced obesity

2014-04-30 | GSE56025 | GEO

Transcription profiling of human osteosarcoma Sa OS cells vs reference RNA of human osteosarcoma U-2 OS cells

Project description:Osteosarcoma (OS) is a common primary bone malignancy that is characterized by high degree of aneuploidy, gene amplification, and multiple unbalanced chromosomal rearrangements. The human osteosarcoma U-2 OS and Sa OS cells lines have been generated more than three decades ago and are used in a wide spectrum of biomedical research. Nevertheless, and despite scattered information about their genetic context, no comprehensive comparative study of their transcriptome profile has been reported to date. The aim of this study was to elucidate common molecular characteristics of the two cell lines as well as differences in their expression profile. Thus the genome wide gene expression profile of the Sa OS cells was compared with reference RNA of U-2 OS cells. These results may provide the basis for future studies and illuminate the molecular differences of the two widely used cell lines.

2009-09-21 | E-MEXP-1897 | biostudies-arrayexpress

U2OS osteosarcoma cells LC-MSMS

Project description:In order to identify the targets of miR-193a-5p in osteosarcoma U2OS cell line, we used a lentivirus-mediated expression system to overexpressing miR-193a precusor, miR-193a-5p target sequence and non-target sequence, respectively, in osteosarcoma cell line U2OS. A tandem mass tag (TMT)-based quantitative proteomic strategy was employed to identify the global profile of miR-193a-5p-regulated proteins. order to identify the targets of miR-193a-5p, we used a lentivirus-mediated expression system to overexpressing miR-193a precusor, miR-193a-5p target sequence and non-target sequence, respectively, in osteosarcoma cell line U2OS. A tandem mass tag (TMT)-based quantitative proteomic strategy was employed to identify the global profile of miR-193a-5p-regulated proteins.

2021-09-08 | PXD013987 | Pride

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