Let-7 microRNAs are developmentally regulated in circulating human erythroid cells

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Let-7 microRNAs are developmentally regulated in circulating human erythroid cells Seung-Jae Noh†1, Samuel H Miller†2, Y Terry Lee1, Sung-Ho Goh1,4, Francesco M Marincola2, David F Stroncek2, Christopher Reed3, Ena Wang2 and Jeffery L Miller*1 Address: 1Molecular Medicine Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA, 2Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA, 3National Naval Medical Center, Department of Obstetrics and Gynecology, Bethesda, Maryland, USA and 4National Cancer Center, Goyang-si, Gyeonggi-do, Republic of Korea Email: Seung-Jae Noh - [email protected]; Samuel H Miller - [email protected]; Y Terry Lee - [email protected]; SungHo Goh - [email protected]; Francesco M Marincola - [email protected]; David F Stroncek - [email protected]; Christopher Reed - [email protected]; Ena Wang - [email protected]; Jeffery L Miller* - [email protected] * Corresponding author †Equal contributors

Published: 25 November 2009 Journal of Translational Medicine 2009, 7:98

doi:10.1186/1479-5876-7-98

Received: 12 November 2009 Accepted: 25 November 2009

This article is available from: http://www.translational-medicine.com/content/7/1/98 © 2009 Noh et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background: MicroRNAs are ~22nt-long small non-coding RNAs that negatively regulate protein expression through mRNA degradation or translational repression in eukaryotic cells. Based upon their importance in regulating development and terminal differentiation in model systems, erythrocyte microRNA profiles were examined at birth and in adults to determine if changes in their abundance coincide with the developmental phenomenon of hemoglobin switching. Methods: Expression profiling of microRNA was performed using total RNA from four adult peripheral blood samples compared to four cord blood samples after depletion of plasma, platelets, and nucleated cells. Labeled RNAs were hybridized to custom spotted arrays containing 474 human microRNA species (miRBase release 9.1). Total RNA from Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines provided a hybridization reference for all samples to generate microRNA abundance profile for each sample. Results: Among 206 detected miRNAs, 79% of the microRNAs were present at equivalent levels in both cord and adult cells. By comparison, 37 microRNAs were up-regulated and 4 microRNAs were down-regulated in adult erythroid cells (fold change > 2; p < 0.01). Among the up-regulated subset, the let-7 miRNA family consistently demonstrated increased abundance in the adult samples by array-based analyses that were confirmed by quan