The miR-28-5p Targetome Discovery Identified SREBF2 as One of the Mediators of the miR-28-5p Tumor Suppressor Activity in Prostate Cancer Cells
by
Sofia Fazio 1,2,†, Gabriele Berti 1,†, Francesco Russo 3,4
, Monica Evangelista 1, Romina D’Aurizio 3, Alberto Mercatanti 1, Marco Pellegrini 3 and Milena Rizzo 1,5,*
Sofia Fazio 1,2,†, Gabriele Berti 1,†, Francesco Russo 3,4, Monica Evangelista 1, Romina D’Aurizio 3, Alberto Mercatanti 1, Marco Pellegrini 3 and Milena Rizzo 1,5,*
1
Non-coding RNA Laboratory, Institute of Clinical Physiology (IFC), CNR, 56124 Pisa, Italy
2
Centre Méditerranéen de Médecin Moléculaire INSERM U1065, Université Côte d’Azur, 06204 Nice, France
3
Institute of Informatics and Telematics (IIT), CNR, 56124 Pisa, Italy
4
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
5
Tuscan Tumor Institute (ITT), 50139 Firenze, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2020, 9(2), 354; https://doi.org/10.3390/cells9020354
Received: 12 December 2019 / Revised: 22 January 2020 / Accepted: 31 January 2020 / Published: 3 February 2020
(This article belongs to the Special Issue microRNA as Therapeutic Target)
miR-28-5p is downregulated in some tumor tissues in which it has been demonstrated to have tumor suppressor (TS) activity. Here, we demonstrate that miR-28-5p acts as a TS in prostate cancer (PCa) cells affecting cell proliferation/survival, as well as migration and invasion. Using the miRNA pull out assay and next generation sequencing, we collected the complete repertoire of miR-28-5p targets, obtaining a data set (miR-28-5p targetome) of 191 mRNAs. Filtering the targetome with TargetScan 7, PITA and RNA22, we found that 61% of the transcripts had miR-28-5p binding sites. To assign a functional value to the captured transcripts, we grouped the miR-28-5p targets into gene families with annotated function and showed that six transcripts belong to the transcription factor category. Among them we selected SREBF2, a gene with an important role in PCa. We validated miR-28-5p/SREBF2 interaction, demonstrating that SREBF2 inhibition affects almost all the tumor processes altered by miR-28-5p re-expression, suggesting that SREBF2 is an important mediator of miR-28-5p TS activity. Our findings support the identification of the targetome of cancer-related miRNAs as a tool to discover genes and pathways fundamental for tumor development, and potential new targets for anti-tumor therapy.
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Keywords:
prostate cancer; miRNA targetome; SREBF2; miR-28-5p; miRNA pull out assay; microRNA
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MDPI and ACS Style
Fazio, S.; Berti, G.; Russo, F.; Evangelista, M.; D’Aurizio, R.; Mercatanti, A.; Pellegrini, M.; Rizzo, M. The miR-28-5p Targetome Discovery Identified SREBF2 as One of the Mediators of the miR-28-5p Tumor Suppressor Activity in Prostate Cancer Cells. Cells 2020, 9, 354.
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