title: Let-7 microRNA and HMGA2 levels of expression are not inversely linked in adipocytic tumors: analysis of 56 lipomas and liposarcomas with molecular cytogenetic data.
abstract: The aim of our study was first to assess the role of HMGA2 expression in the pathogenesis of adipocytic tumors (AT) and, second, to seek a potential correlation between overexpression of HMGA2 and let-7 expression inhibition by analyzing a series of 56 benign and malignant AT with molecular cytogenetic data. We measured the levels of expression of HMGA2 mRNA and of eight members of the let-7 microRNA family using quantitative RT-PCR and expression of HMGA2 protein using immunohistochemistry. HMGA2 was highly overexpressed in 100% of well-differentiated/dedifferentiated liposarcomas (WDLPS/DDLPS), all with HMGA2 amplification, and 100% of lipomas with HMGA2 rearrangement. Overexpression of HMGA2 mRNA was detected in 76% of lipomas without HMGA2 rearrangement. HMGA2 protein expression was detected in 100% of lipomas with HMGA2 rearrangement and 48% of lipomas without HMGA2 rearrangement. We detected decreased expression levels of some let-7 members in a significant proportion of AT. Notably, let-7b and let-7g were inhibited in 61% of WDLPS/DDLPS. In lipomas, each type of let-7 was inhibited in approximately one-third of the cases. Although overexpression of both HMGA2 mRNA and protein in a majority of ordinary lipomas without HMGA2 structural rearrangement may have suggested a potential role for let-7 microRNAs, we did not observe a significant link with let-7 inhibition in such cases. Our results indicate that inhibition of let-7 microRNA expression may participate in the deregulation of HMGA2 in AT but that this inhibition is neither a prominent stimulator for HMGA2 overexpression nor a surrogate to genomic HMGA2 rearrangements.
authors.affiliation: Laboratory of Solid Tumors Genetics, Nice University Hospital, Nice, France. laurence.bianchini@unice.fr
authors.forename: Laurence
authors.initials: L
authors.lastname: Bianchini
authors.forename: Esma
authors.initials: E
authors.lastname: Saâda
authors.forename: Elisabet
authors.initials: E
authors.lastname: Gjernes
authors.forename: Marion
authors.initials: M
authors.lastname: Marty
authors.forename: Juliette
authors.initials: J
authors.lastname: Haudebourg
authors.forename: Isabelle
authors.initials: I
authors.lastname: Birtwisle-Peyrottes
authors.forename: Frédérique
authors.initials: F
authors.lastname: Keslair
authors.forename: Bérangère
authors.initials: B
authors.lastname: Chignon-Sicard
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chamorey
authors.forename: Florence
authors.initials: F
authors.lastname: Pedeutour
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D007223:Infant; D008067:Lipoma / Q000235:genetics* / Q000473:pathology; D008080:Liposarcoma / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged
chemical_list: D025743:HMGA2 Protein; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human