期刊
CELLS
卷 9, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/cells9020354
关键词
prostate cancer; miRNA targetome; SREBF2; miR-28-5p; miRNA pull out assay; microRNA
类别
资金
- Istituto Toscano Tumori
- Italian Ministry of Education and University (MIUR) [PRIN 201534HNXC]
- BRIDGE-Translational Excellence Programme (bridge.ku.dk), Faculty of Health and Medical Sciences, University of Copenhagen - Novo Nordisk Foundation [NNF18SA0034956]
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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