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MiRNA expression profiles of multiple myeloma

ABSTRACT: miRNA expression profiles of multiple myeloma

PROVIDER: PRJNA668113 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12795565.fastq.gz	Fastqsanger.gz
	SRR12795566.fastq.gz	Fastqsanger.gz
	SRR12795567.fastq.gz	Fastqsanger.gz
	SRR12795568.fastq.gz	Fastqsanger.gz
	SRR12795569.fastq.gz	Fastqsanger.gz

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miRNA expression profiles of multiple myeloma

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Project description:miRNA profiling in multiple myeloma - microRNAs represent a class of noncoding regulators of gene expression implicated in several biological and pathophysiological processes, including cancer. We investigate here their role in multiple myeloma using miChip-arrays interrogating 559 miRNAs in 92 purified myeloma-, MGUS-, normal plasma cell- and myeloma cell line samples. Impact on gene expression is assessed by Affymetrix U133 2.0 DNA-microarrays in 741 samples including two cohorts of 332 and 345 myeloma patients; chromosomal aberrations are assessed by iFISH, survival for 247 and 345 patients undergoing up-front high-dose therapy and autologous stem cell transplantation. Compared to normal plasma cells, 67/559 (12%) miRNAs are differentially expressed with fold changes of 4.6 to -3.1 in myeloma-, 20 (3.6%) in MGUS-samples, and three (0.5%) between MGUS- and myeloma-samples. Expression of miRNAs is associated with biological and pathophysiological parameters, i.e. proliferation, chromosomal aberrations, e.g. t(4;14), tumor mass, and gene expression-based high-risk scores. This holds true for target-gene signatures of regulated mRNAs. miRNA-expression confers prognostic significance for event-free (72/559) and overall survival (69/559), as do respective target-gene signatures. In conclusion, the miRNome of myeloma confers a pattern of small changes of individual miRNAs compared to normal plasma cells impacting on gene expression, biological functions, and survival.

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Project description:We used microarray analyses of patient myeloma cells (n=52) to correlate individual miRNA expression profiles with GEP-based risk defined by mRNA expression profilesx as well as clinical features of the disease. Unlike for mRNAs, genome-wide elevation of miRNA expression patterns were significantly positively associated with a mRNA-based GEP-risk score (P <.01) and proliferation index (P <.05). Consistent with our observation of global deregulation of miRNA expression profiles, silencing EIF2C2/AGO2, a gene component of the mRNA-based high-risk signature and a master regulator of the genesis and functionality of all miRNAs, dramatically decreased viability in myeloma cell lines. mRNA expression profiling: We performed protein-coding gene expression profiles of myeloma cells from newly diagnosed patients with different molecularly defined disease types. miRNA expression profiling: We used microarray analyses of patient myeloma cells (n=52) to correlate individual miRNA expression profiles with GEP-based risk defined by mRNA expression profiles as well as clinical features of the disease.

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