MicroRNA expression changes during human leukemic HL-60 cell differentiation induced by 4-hydroxynonenal, a product of lipid peroxidation.
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.
Pizzimenti
Stefania
S
Dipartimento di Medicina e Oncologia Sperimentale, Sezione di Patologia Generale, Università di Torino, Corso Raffaello 30, 10125 Torino, Italy. stefania.pizzimenti@unito.it
Ferracin
Manuela
M
Sabbioni
Silvia
S
Toaldo
Cristina
C
Pettazzoni
Piergiorgio
P
Dianzani
Mario Umberto
MU
Negrini
Massimo
M
Barrera
Giuseppina
G
D000447:Aldehydes / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018390:Gene Targeting; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015533:Transcriptional Activation
D000447:Aldehydes; C569392:MIRN202 microRNA, human; C526012:MIRN378 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; C490764:SUFU protein, human; C027576:4-hydroxy-2-nonenal