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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.

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Author information

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).

Conflict of interest

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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Keywords

  • miRNAs
  • Mucoepidermoid carcinoma
  • Pleomorphic adenoma
  • Apoptosis
  • Real-time PCR