Integrating miRNA and Gene Expression Profiling Analysis Revealed Regulatory Networks in Gastrointestinal Stromal Tumors

Abstract

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.

Keywords::

• GIST
• IGF1R
• KIT
• let-7b
• miR139-5p
• miR-455-5p
• PDGFRA
• WT-SDH deficient

Acknowledgements

Special thanks to the GIST Study Group members, University of Bologna, Bologna, Italy: A Altimari, R Casadio, P Castellucci, F Catena, M Del Gaudio, A D’Errico, M Di Battista, G Ercolani, S Fanti, M Fiorentino, WF Grigioni, E Gruppioni, M Ianni, PL Martelli, A Mandrioli, N Pagano, AD Pinna, MG Pirini, P Tomassetti, V Di Scioscio and M Zompatori.

Financial & competing interests disclosure

The study was supported by a financial contribution of the AIG (Associazione Italiana GIST) and the AIRC (Associazione Italiana Ricerca sul Cancro; Pantaleo MA My First Grant 2013). G Ravegnini has been supported by Fondazione Umberto Veronesi, and is now supported by the Department of Pharmacy and Biotechnology, the University of Bologna. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was approved by the local institutional ethical committee of Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi (approval number 113/2008/U/Tess). All patients provided written informed consent.

Additional information

Funding

The study was supported by a financial contribution of the AIG (Associazione Italiana GIST) and the AIRC (Associazione Italiana Ricerca sul Cancro; Pantaleo MA My First Grant 2013). G Ravegnini has been supported by Fondazione Umberto Veronesi, and is now supported by the Department of Pharmacy and Biotechnology, the University of Bologna. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.