TY - JOUR
T1 - MicroRNA expression changes during human leukemic HL-60 cell differentiation induced by 4-hydroxynonenal, a product of lipid peroxidation
AU - Pizzimenti, Stefania
AU - Ferracin, Manuela
AU - Sabbioni, Silvia
AU - Toaldo, Cristina
AU - Pettazzoni, Piergiorgio
AU - Dianzani, Mario Umberto
AU - Negrini, Massimo
AU - Barrera, Giuseppina
N1 - Funding Information:
This work was supported by grants from Compagnia di San Paolo, Turin (Italy), to G.B. and by grants from the Italian Ministry of University, the Italian Ministry of Health, and the Associazione Italiana per la Ricerca sul Cancro to M.N. M.F. is a recipient of a fellowship from the Fondazione Italiana per la Ricerca sul Cancro. We thank Prof. Michele Caselle and Dr. Davide Corà from the Dept of Theoretical Physics and INFN, University of Turin for their scientific support.
PY - 2009/1/15
Y1 - 2009/1/15
N2 - 4-Hydroxynonenal (HNE) is one of several lipid oxidation products that may have an impact on human pathophysiology. It is an important second messenger involved in the regulation of various cellular processes and exhibits antiproliferative and differentiative properties in various tumor cell lines. The mechanisms by which HNE affects cell growth and differentiation are only partially clarified. Because microRNAs (miRNAs) have the ability to regulate several cellular processes, we hypothesized that HNE, in addition to other mechanisms, could affect miRNA expression. Here, we present the results of a genome-wide miRNA expression profiling of HNE-treated HL-60 leukemic cells. Among 470 human miRNAs, 10 were found to be differentially expressed between control and HNE-treated cells (at p < 0.05). Six miRNAs were down-regulated (miR-181a*, miR-199b, miR-202, miR-378, miR-454-3p, miR-575) and 4 were up-regulated (miR-125a, miR-339, miR-663, miR-660). Three of these regulated miRNAs (miR-202, miR-339, miR-378) were further assayed and validated by quantitative real-time RT-PCR. Moreover, consistent with the down-regulation of miR-378, HNE also induced the expression of the SUFU protein, a tumor suppressor recently identified as a target of miR-378. The finding that HNE could regulate the expression of miRNAs and their targets opens new perspectives on the understanding of HNE-controlled pathways. A functional analysis of 191 putative gene targets of miRNAs modulated by HNE is discussed.
AB - 4-Hydroxynonenal (HNE) is one of several lipid oxidation products that may have an impact on human pathophysiology. It is an important second messenger involved in the regulation of various cellular processes and exhibits antiproliferative and differentiative properties in various tumor cell lines. The mechanisms by which HNE affects cell growth and differentiation are only partially clarified. Because microRNAs (miRNAs) have the ability to regulate several cellular processes, we hypothesized that HNE, in addition to other mechanisms, could affect miRNA expression. Here, we present the results of a genome-wide miRNA expression profiling of HNE-treated HL-60 leukemic cells. Among 470 human miRNAs, 10 were found to be differentially expressed between control and HNE-treated cells (at p < 0.05). Six miRNAs were down-regulated (miR-181a*, miR-199b, miR-202, miR-378, miR-454-3p, miR-575) and 4 were up-regulated (miR-125a, miR-339, miR-663, miR-660). Three of these regulated miRNAs (miR-202, miR-339, miR-378) were further assayed and validated by quantitative real-time RT-PCR. Moreover, consistent with the down-regulation of miR-378, HNE also induced the expression of the SUFU protein, a tumor suppressor recently identified as a target of miR-378. The finding that HNE could regulate the expression of miRNAs and their targets opens new perspectives on the understanding of HNE-controlled pathways. A functional analysis of 191 putative gene targets of miRNAs modulated by HNE is discussed.
KW - 4-Hydroxynonenal
KW - Differentiation
KW - Free radicals
KW - HL-60 leukemic cells
KW - Microarray
KW - SUFU
KW - hsa-miR-202
KW - hsa-miR-339
KW - hsa-miR-378
KW - miRNA
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U2 - 10.1016/j.freeradbiomed.2008.10.035
DO - 10.1016/j.freeradbiomed.2008.10.035
M3 - Article
C2 - 19022373
AN - SCOPUS:58049100243
SN - 0891-5849
VL - 46
SP - 282
EP - 288
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 2
ER -