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Altered expression of apoptosis-regulating miRNAs in salivary gland tumors suggests their involvement in salivary gland tumorigenesis

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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.

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Authors and Affiliations

  1. Centro Internacional de Pesquisa, A.C.Camargo Cancer Center, Rua Taguá, 440–Primeiro andar, São Paulo, 01508-010, Brazil

    Bianca de Cássia Troncarelli de Campos Parra Flores, Aline Santos Damascena & Cláudia Malheiros Coutinho-Camillo

  2. Department of General Pathology, Dental School, University of São Paulo, São Paulo, Brazil

    Silvia Vanessa Lourenço & Fernando Augusto Soares

  3. Department of Head and Neck Surgery and Otorhinolaryngology, A.C.Camargo Cancer Center, São Paulo, Brazil

    Luiz Paulo Kowaslki

  4. Department of Anatomic Pathology, A.C.Camargo Cancer Center, São Paulo, SP, Brazil

    Fernando Augusto Soares & Cláudia Malheiros Coutinho-Camillo

Authors
  1. Bianca de Cássia Troncarelli de Campos Parra Flores
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  2. Silvia Vanessa Lourenço
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  3. Aline Santos Damascena
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  4. Luiz Paulo Kowaslki
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  5. Fernando Augusto Soares
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  6. Cláudia Malheiros Coutinho-Camillo
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Corresponding author

Correspondence to Cláudia Malheiros Coutinho-Camillo.

Ethics declarations

The Ethics Committee of the A.C.Camargo Cancer Center approved the study on October 22, 2013 (protocol number 1578/11E).

Funding

The study was supported by grants 11/02051-6 and 12/09759-7, São Paulo Research Foundation (FAPESP). The authors were supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; scholarship to BCTCPF).

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The authors declare that they have no conflict of interest.

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Flores, B.d.C.T.d.C.P., Lourenço, S.V., Damascena, A.S. et al. Altered expression of apoptosis-regulating miRNAs in salivary gland tumors suggests their involvement in salivary gland tumorigenesis. Virchows Arch 470, 291–299 (2017). https://doi.org/10.1007/s00428-016-2049-z

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  • DOI: https://doi.org/10.1007/s00428-016-2049-z

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