Integrating miRNA and gene expression profiling analysis revealed regulatory networks in gastrointestinal stromal tumors.
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.



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.



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.



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.
'Giorgio Prodi' Cancer Research Center, University of Bologna, Bologna, Italy.|Department of Specialized, Experimental & Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
Maria Abbondanza
MA
Pantaleo
Department of Pharmacy & Biotechnology, Via Irnerio 48, 40126 Bologna, Italy.
Gloria
G
Ravegnini
'Giorgio Prodi' Cancer Research Center, University of Bologna, Bologna, Italy.
Annalisa
A
Astolfi
Laboratory of Pre-Clinical & Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (PZ), Italy.
Vittorio
V
Simeon
Department of Specialized, Experimental & Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
Margherita
M
Nannini
Department of Specialized, Experimental & Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
Maristella
M
Saponara
Department of Specialized, Experimental & Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
Milena
M
Urbini
Department of Specialized, Experimental & Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
Lidia
L
Gatto
Department of Specialized, Experimental & Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
Valentina
V
Indio
Department of Pharmacy & Biotechnology, Via Irnerio 48, 40126 Bologna, Italy.
Giulia
G
Sammarini
Pathology Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Donatella
D
Santini
Department of Specialized, Experimental & Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
Manuela
M
Ferracin
Department of Morphology, Surgery & Experimental Medicine, University of Ferrara, Ferrara, Italy.
Massimo
M
Negrini
Department of Pharmacy & Biotechnology, Via Irnerio 48, 40126 Bologna, Italy.
Patrizia
P
Hrelia
'Giorgio Prodi' Cancer Research Center, University of Bologna, Bologna, Italy.|Department of Specialized, Experimental & Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
Guido
G
Biasco
Department of Pharmacy & Biotechnology, Via Irnerio 48, 40126 Bologna, Italy.
Sabrina
S
Angelini
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D017526:Receptor, IGF Type 1; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D017451:Receptors, Somatomedin / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
C000597236:IGF1R protein, human; D035683:MicroRNAs; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D013385:Succinate Dehydrogenase; D019009:Proto-Oncogene Proteins c-kit; D017526:Receptor, IGF Type 1; D020796:Receptor, Platelet-Derived Growth Factor alpha; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6
GIST; IGF1R; KIT; PDGFRA; WT-SDH deficient; let-7b; miR-455-5p; miR139-5p