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Integrated analysis of miRNA and mRNA during differentiation of human CD34+ cells delineates the regulatory roles of microRNA in hematopoiesis.

ABSTRACT: In the process of human hematopoiesis, precise regulation of the expression of lineage-specific gene products is critical for multiple cell-fate decisions that govern cell differentiation, proliferation, and self-renewal. Given the important role of microRNAs (miRNAs) in development and differentiation, we examined the global expression of miRNA in CD34(+) cells during lineage specific hematopoiesis and found 49 miRNAs to be differentially expressed, with functional roles in cellular growth and proliferation, and apoptosis. miR-18a was upregulated during erythropoiesis and downregulated during megakaryopoiesis. miR-145 was upregulated during granulopoiesis and down regulated during erythropoiesis. Megakaryopoitic differentiation resulted in significant alteration in the expression of many miRNAs that are believed to play critical roles in the regulation of B and T cell differentiation. Target prediction analyses on three different miRNA databases indicated that TargetScan outperformed microCosm and miRDB in identifying potential miRNA targets associated with hematopoietic differentiation process. An integrated analysis of the observed miRNAs and messenger RNAs (mRNAs) resulted in 87 highly correlated miRNA-mRNA pairs that have major functional roles in cellular growth and proliferation, hematopoietic system development, and Wnt/B-catenin and Flt 3 signaling pathways. We believe that this study will enhance our understanding on the regulatory roles of miRNA in hematopoiesis by providing a library of mRNA-miRNA networks.

SUBMITTER: Raghavachari N

PROVIDER: S-EPMC3878057 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Integrated analysis of miRNA and mRNA during differentiation of human CD34+ cells delineates the regulatory roles of microRNA in hematopoiesis.

Raghavachari Nalini N Liu Poching P Barb Jennifer J JJ Yang Yanqin Y Wang Richard R Nguyen Quang Tri QT Munson Peter J PJ

Experimental hematology 20131016 1

In the process of human hematopoiesis, precise regulation of the expression of lineage-specific gene products is critical for multiple cell-fate decisions that govern cell differentiation, proliferation, and self-renewal. Given the important role of microRNAs (miRNAs) in development and differentiation, we examined the global expression of miRNA in CD34(+) cells during lineage specific hematopoiesis and found 49 miRNAs to be differentially expressed, with functional roles in cellular growth and ...[more]

PMID: 24139908

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Project description:BackgroundAccumulating evidences demonstrated that microRNA-target gene pairs were closely related to tumorigenesis and development. However, the correlation between miRNA and target gene was insufficiently understood, especially its changes between tumor and normal tissues.ObjectivesThe aim of this study was to evaluate the changes of correlation of miRNAs-target pairs between normal and tumor.Materials and methods5680 mRNA and 5740 miRNA expression profiles of 11 major human cancers were downloaded from the Cancer Genome Atlas (TCGA). The 11 cancer types were bladder urothelial carcinoma, breast invasive carcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, and thyroid carcinoma. For each cancer type, we firstly obtained differentially expressed miRNAs (DEMs) and genes (DEGs) in tumor and then acquired critical miRNA-target gene pairs by combining DEMs, DEGs and two experimentally validated miRNA-target interaction databases, miRTarBase and miRecords. We collected samples with both miRNA and mRNA expression values and performed a correlation analysis by Pearson method for miRNA-target pairs in normal and tumor, respectively.ResultsWe totally got 4743 critical miRNA-target pairs across 11 cancer types, and 4572 of them showed weaker correlation in tumor than in normal. The average correlation coefficients of miRNA-target pairs were different greatly between normal (-0.38 ~ -0.61) and tumor (-0.04 ~ -0.26) for 11 cancer type. The pan-cancer network, which consisted of 108 edges connecting 35 miRNAs and 89 target genes, showed the interactions of pairs appeared in multicancers.ConclusionsThis comprehensive analysis revealed that correlation between miRNAs and target genes was greatly reduced in tumor and these critical pairs we got were involved in cellular adhesion, proliferation, and migration. Our research could provide opportunities for investigating cancer molecular regulatory mechanism and seeking therapeutic targets.

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Integrated analysis of miRNA and mRNA during differentiation of human CD34+ cells delineates the regulatory roles of microRNA in hematopoiesis.

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Integrated analysis of miRNA and mRNA during differentiation of human CD34+ cells delineates the regulatory roles of microRNA in hematopoiesis.

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