Journal
EPIGENOMICS
Volume 8, Issue 10, Pages 1347-1366Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/epi-2016-0030
Keywords
GIST; IGF1R; KIT; let-7b; miR139-5p; miR-455-5p; PDGFRA; WT-SDH deficient
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Funding
- AIG (Associazione Italiana GIST)
- AIRC (Associazione Italiana Ricerca sul Cancro
- Pantaleo MA My First Grant)
- Fondazione Umberto Veronesi
- Department of Pharmacy and Biotechnology, the University of Bologna
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Aim: Currently, little is known about differences in miRNA expression between KIT/PDGFRA mutant and KIT/PDGFRA wild-type (WT)-SDH deficient gastrointestinal stromal tumors (GIST). This prompted us to perform an integrated multiple expression profile of miRNA and mRNA, constructing an original miRNA-mRNA regulatory network in KIT/PDGFRA WT-SDH deficient GIST patients. Patients & methods: Analyses were carried out on KIT/PDGFRA mutant versus KIT/PDGFRA WT-SDH deficient GIST. Genome-wide miRNA and gene-expression analysis were performed using Agilent Human miRNA microarray and Affimetrix array, respectively. Results: Three potential regulatory networks (IGF1R -> miR-139-5p/miR-455/let-7b, cyclin-dependent kinase 6 (CDK6) -> miR-139-5p/let-7b and CD44 -> miR-330-3p) were identified. Conclusion: The miR-139-5p, 455-5p and let-7b signature, in particular, may represent an important therapeutic target in KIT/PDGFRA WT-SDH deficient GIST, usually characterized by IGF1R overexpression.
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