TY - JOUR
T1 - Multitargeting activity of miR-24 inhibits long-term melatonin anticancer effects
AU - Mori, Federica
AU - Ferraiuolo, Maria
AU - Santoro, Raffaela
AU - Sacconi, Andrea
AU - Goeman, Frauke Inger Karen
AU - Pallocca, Matteo
AU - Pulito, Claudio
AU - Korita, Etleva
AU - Fanciulli, Maurizio
AU - Muti, Paola
AU - Blandino, Giovanni
AU - Strano, Sabrina
N1 - STRANO e BLANDINO in doppia affiliazione IRe/Mac Master University
PY - 2016/4/12
Y1 - 2016/4/12
N2 - We have previously shown that melatonin exerts tumor suppressor activities by inducing the p38-p53 axis. This occurred within a few hours while no data are available on how melatonin pathway can be sustained on the long term. Here we show that miR-24, which has been demonstrated to target genes involved in the DNA repair process, targets p38, p53, PML and H2AX simultaneously. We show that long-term treatment with melatonin can decrease miR-24 levels post-transcriptionally, which pairs with a long-wave regulation of genes involved in cell proliferation, DNA damage, RNA metabolism and cell shape and transformation. Moreover, we show that melatonin can inhibit cell proliferation and migration, at least in part, by downregulating miR-24. Furthermore, we propose the involvement of hnRNP A1, which is downregulated by melatonin and involved in miRNA processing, in the regulation of miR-24 levels by melatonin. We conclude showing that miR-24 is upregulated in colon, breast and head and neck datasets and its levels negatively correlate with overall survival.
AB - We have previously shown that melatonin exerts tumor suppressor activities by inducing the p38-p53 axis. This occurred within a few hours while no data are available on how melatonin pathway can be sustained on the long term. Here we show that miR-24, which has been demonstrated to target genes involved in the DNA repair process, targets p38, p53, PML and H2AX simultaneously. We show that long-term treatment with melatonin can decrease miR-24 levels post-transcriptionally, which pairs with a long-wave regulation of genes involved in cell proliferation, DNA damage, RNA metabolism and cell shape and transformation. Moreover, we show that melatonin can inhibit cell proliferation and migration, at least in part, by downregulating miR-24. Furthermore, we propose the involvement of hnRNP A1, which is downregulated by melatonin and involved in miRNA processing, in the regulation of miR-24 levels by melatonin. We conclude showing that miR-24 is upregulated in colon, breast and head and neck datasets and its levels negatively correlate with overall survival.
KW - Melatonin
KW - MiR-24
KW - P53
KW - PML
KW - RNA-Seq
UR - http://www.scopus.com/inward/record.url?scp=84964757107&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964757107&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.7978
DO - 10.18632/oncotarget.7978
M3 - Article
AN - SCOPUS:84964757107
VL - 7
SP - 20532
EP - 20548
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 15
ER -