Multitargeting activity of miR-24 inhibits long-term melatonin anticancer effects

作者：Mori Federica; Ferraiuolo Maria; Santoro Raffaela; Sacconi Andrea; Goeman Frauke; Pallocca Matteo; Pulito Claudio; Korita Etleva; Fanciulli Maurizio; Muti Paola; Blandino Giovanni; Strano Sabrina

来源：Oncotarget, 2016, 7(15): 20532-20548.

DOI：10.18632/oncotarget.7978

• melatonin
• miR-24
• RNA-Seq
• p53
• PML

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.

• 出版日期2016-4-12