title: Altered expression of apoptosis-regulating miRNAs in salivary gland tumors suggests their involvement in salivary gland tumorigenesis.
abstract: Salivary gland tumors comprise a heterogeneous group of lesions with different histological features and diverse clinical pathophysiology. They account for about 3% of all head and neck tumors. Apoptosis plays an important role during morphogenesis of glandular structures, including that of the salivary gland. Recent studies have demonstrated that several microRNAs (miRNAs) are involved in the control of apoptosis. The aim of the present study was to determine the expression of apoptosis-related miRNAs (miR-15a, miR-16, miR-17-5p, miR-20a, miR-21, miR-29, and miR-34) and their target mRNAs in 25 pleomorphic adenomas, 23 mucoepidermoid carcinomas, and 10 non-neoplastic salivary gland samples by real-time RT-PCR. We observed upregulation of miR-15a, miR-16, miR-17-5p, miR-21, miR-29, and miR-34a in pleomorphic adenomas. The expression of miR-21 and miR-34a was upregulated in 91 and 74% of mucoepidermoid carcinomas, respectively. Downregulation of miR-20a was observed in 75% of pleomorphic adenomas and in 57% of mucoepidermoid carcinomas. APAF1, BAX, BCL2, BID, CASP2, CASP8, DIABLO , and TP53 transcripts were upregulated in both tumor types. BAD transcripts were upregulated in pleomorphic adenomas. CASP3 and CASP6 transcripts were upregulated in mucoepidermoid carcinomas. BCL2, CASP2, CASP6, and CASP8 proteins were mostly absent in mucoepidermoid carcinomas but expressed in few cells in pleomorphic adenomas. Our study provides evidence of alterations in the expression of apoptosis-regulating miRNAs in salivary gland tumors, suggesting possible involvement of these microRNAs in salivary gland tumorigenesis.
authors.affiliation: Centro Internacional de Pesquisa, A.C.Camargo Cancer Center, Rua Taguá, 440-Primeiro andar, São Paulo, 01508-010, Brazil.
authors.forename: Bianca de Cássia Troncarelli de Campos Parra
authors.initials: BC
authors.lastname: Flores
authors.affiliation: Department of General Pathology, Dental School, University of São Paulo, São Paulo, Brazil.
authors.forename: Silvia Vanessa
authors.initials: SV
authors.lastname: Lourenço
authors.affiliation: Centro Internacional de Pesquisa, A.C.Camargo Cancer Center, Rua Taguá, 440-Primeiro andar, São Paulo, 01508-010, Brazil.
authors.forename: Aline Santos
authors.initials: AS
authors.lastname: Damascena
authors.affiliation: Department of Head and Neck Surgery and Otorhinolaryngology, A.C.Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowaslki
authors.affiliation: Department of General Pathology, Dental School, University of São Paulo, São Paulo, Brazil.|Department of Anatomic Pathology, A.C.Camargo Cancer Center, São Paulo, SP, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Centro Internacional de Pesquisa, A.C.Camargo Cancer Center, Rua Taguá, 440-Primeiro andar, São Paulo, 01508-010, Brazil. ccamilo@cipe.accamargo.org.br.|Department of Anatomic Pathology, A.C.Camargo Cancer Center, São Paulo, SP, Brazil. ccamilo@cipe.accamargo.org.br.
authors.forename: Cláudia Malheiros
authors.initials: CM
authors.lastname: Coutinho-Camillo
mesh_terms: D008949:Adenoma, Pleomorphic / Q000473:pathology*; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D018277:Carcinoma, Mucoepidermoid / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs
keywords: Apoptosis; Mucoepidermoid carcinoma; Pleomorphic adenoma; Real-time PCR; miRNAs