BACKGROUND: A keratocystic odontogenic tumor (KCOT) is a benign destructive recurrent odontogenic cystic neoplasm. The microRNAs (miRNAs) miR-15a and miR-16-1 function as negative regulators of the anti-apoptotic gene BCL2 at the post-transcriptional level. Notably, high Bcl-2 immunoexpression is found in the epithelial lining of KCOTs, while the loss of Bcl-2 immunopositive cells is observed in marsupialized cysts. The purpose of this study was to investigate whether the transcription of miR-15a and miR-16-1 is altered in KCOTs and whether it is associated with BCL2 gene expression in such lesions. METHODS: Using qRT-PCR and immunohistochemical analyses, we examined miR-15a/16-1 and BCL2 gene expression in KCOTs. The impact of miR-15a/16-1 expression on BCL2 gene translation was investigated by in vitro studies using primary KCOT culture cells. RESULTS: Using qRT-PCR, we observed miR-15a and/or miR-16-1 downregulation in the majority of the KCOT samples (24 of 28). We also observed higher BCL2 mRNA expression in 19 of 20 KCOT frozen samples and moderate to high Bcl-2 immunopositivity in the basal layer cells of 16 of 18 paraffin embedded KCOTs (median: 42.6 %). In vitro over-expression of miR-15a/16-1 in human KCOT-1 primary cell cultures resulted in a decrease in Bcl-2 protein expression. Furthermore, all five paired KCOTs collected before and after marsupialization treatment exhibited an increase in miR-15a after the procedure. CONCLUSIONS: Our results suggest that KCOT neoplastic cells exhibit an anti-apoptotic profile that may be related to lower miR-15a/16-1 expression. Additionally, we demonstrated that miRNA expression increases after marsupialization, implicating an etiological and therapeutic role of miRNAs in KCOT.
BACKGROUND: A keratocystic odontogenic tumor (KCOT) is a benign destructive recurrent odontogenic cystic neoplasm. The microRNAs (miRNAs) miR-15a and miR-16-1 function as negative regulators of the anti-apoptotic gene BCL2 at the post-transcriptional level. Notably, high Bcl-2 immunoexpression is found in the epithelial lining of KCOTs, while the loss of Bcl-2 immunopositive cells is observed in marsupialized cysts. The purpose of this study was to investigate whether the transcription of miR-15a and miR-16-1 is altered in KCOTs and whether it is associated with BCL2 gene expression in such lesions. METHODS: Using qRT-PCR and immunohistochemical analyses, we examined miR-15a/16-1 and BCL2 gene expression in KCOTs. The impact of miR-15a/16-1 expression on BCL2 gene translation was investigated by in vitro studies using primary KCOT culture cells. RESULTS: Using qRT-PCR, we observed miR-15a and/or miR-16-1 downregulation in the majority of the KCOT samples (24 of 28). We also observed higher BCL2 mRNA expression in 19 of 20 KCOT frozen samples and moderate to high Bcl-2 immunopositivity in the basal layer cells of 16 of 18 paraffin embedded KCOTs (median: 42.6 %). In vitro over-expression of miR-15a/16-1 in human KCOT-1 primary cell cultures resulted in a decrease in Bcl-2 protein expression. Furthermore, all five paired KCOTs collected before and after marsupialization treatment exhibited an increase in miR-15a after the procedure. CONCLUSIONS: Our results suggest that KCOT neoplastic cells exhibit an anti-apoptotic profile that may be related to lower miR-15a/16-1 expression. Additionally, we demonstrated that miRNA expression increases after marsupialization, implicating an etiological and therapeutic role of miRNAs in KCOT.
Authors: Peter S Linsley; Janell Schelter; Julja Burchard; Miho Kibukawa; Melissa M Martin; Steven R Bartz; Jason M Johnson; Jordan M Cummins; Christopher K Raymond; Hongyue Dai; Nelson Chau; Michele Cleary; Aimee L Jackson; Michael Carleton; Lee Lim Journal: Mol Cell Biol Date: 2007-01-22 Impact factor: 4.272
Authors: George Adrian Calin; Calin Dan Dumitru; Masayoshi Shimizu; Roberta Bichi; Simona Zupo; Evan Noch; Hansjuerg Aldler; Sashi Rattan; Michael Keating; Kanti Rai; Laura Rassenti; Thomas Kipps; Massimo Negrini; Florencia Bullrich; Carlo M Croce Journal: Proc Natl Acad Sci U S A Date: 2002-11-14 Impact factor: 11.205
Authors: C Ren; M G Diniz; C Piazza; H M Amm; D L Rollins; H Rivera; P Devilliers; D P Kestler; P D Waite; O A Mamaeva; M Macdougall Journal: Cells Tissues Organs Date: 2011-05-19 Impact factor: 2.481
Authors: Eliane Macedo Sobrinho Santos; Hércules Otacílio Santos; Ivoneth Dos Santos Dias; Sérgio Henrique Santos; Alfredo Maurício Batista de Paula; John David Feltenberger; André Luiz Sena Guimarães; Lucyana Conceição Farias Journal: Int J Mol Cell Med Date: 2016-12-06
Authors: Ravi Nimmanagoti; Srk Nandan; Pavan G Kulkarni; Shyam Prasad Reddy; M Keerthi; Gouri Pupala Journal: Int J Appl Basic Med Res Date: 2019 Jan-Mar