Multitargeting activity of miR-24 inhibits long-term melatonin anticancer effects
Metrics: PDF 1999 views | HTML 2812 views | ?
Federica Mori1,*, Maria Ferraiuolo1,2,*, Raffaela Santoro1,*, Andrea Sacconi2, Frauke Goeman2, Matteo Pallocca3, Claudio Pulito1, Etleva Korita1, Maurizio Fanciulli3, Paola Muti4, Giovanni Blandino2,4, Sabrina Strano1,4
1Molecular Chemoprevention Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, 00144 Rome, Italy
2Translational Oncogenomics Unit, Molecular Medicine Area, Regina Elena National Cancer Institute, 00144 Rome, Italy
3Department of Research, Advanced Diagnostics and Technological Innovation, Translational Research Area, Regina Elena National Cancer Institute, 00144 Rome, Italy
4Department of Oncology, Juravinski Cancer Center-McMaster University, Hamilton, ON L8V 5C2, Ontario, Canada
*These authors contributed equally to this work
Giovanni Blandino, e-mail: [email protected]
Sabrina Strano, e-mail: [email protected]
Keywords: melatonin, miR-24, RNA-Seq, p53, PML
Received: November 19, 2015 Accepted: February 11, 2016 Published: March 08, 2016
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.