title: Expression of apoptosis-regulating miRNAs and target mRNAs in oral squamous cell carcinoma.
abstract: Aberrations in the apoptotic mechanisms that cause excessive or deficient programmed cell death have been linked to a wide array of pathological conditions. In this study, using real-time reverse transcriptase-PCR, we analyzed the expression of apoptosis-regulating miRNAs (miR-15a, miR-16, miR-17-5p, miR-20a, miR-21, miR-29a, and miR-34a) in 20 oral squamous cell carcinoma and 5 normal oral mucosa tissue samples. Bioinformatic algorithms were used to identify the target genes of these miRNAs (BCL2, CASP2, CASP7, CASP8, DIABLO). The expression transcript levels of the target genes were measured in 50 oral squamous cell carcinoma and 10 normal oral mucosa tissue samples. We observed downregulation of miR-15a, miR-29a, and miR-34a in 50, 75, and 70% of samples, respectively. miR-16, miR-17-5p, miR-20a, and miR-21 expression was normal in 80, 75, 90, and 60% of samples, respectively. BCL2 transcripts were downregulated in 60% of samples, and normal-like expression was observed for CASP2, CASP7, CASP8, and DIABLO transcripts in 66, 82, 68, and 60% of samples, respectively. BCL2 expression was negative to weak, and that of proteins CASP2, CASP7, CASP8, and DIABLO was moderate to strong. Our study provides evidence of alterations in the expression of apoptosis-regulating miRNAs and genes in the apoptotic pathway, demonstrating that regulation of apoptosis is a hallmark of oral squamous cell carcinoma pathogenesis.
authors.affiliation: Department of Anatomic Pathology, AC Camargo Cancer Center, São Paulo, Brazil. Electronic address: cmccamillo@gmail.com.
authors.forename: Cláudia Malheiros
authors.initials: CM
authors.lastname: Coutinho-Camillo
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: Interinstitutional Graduate Program on Bioinformatics, University of São Paulo, São Paulo, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: de Araújo Lima
authors.affiliation: Department of Head and Neck Surgery and Otorhinolaryngology, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
authors.affiliation: Department of Anatomic Pathology, AC Camargo Cancer Center, São Paulo, Brazil; Department of General Pathology, Dental School, University of São Paulo, São Paulo, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D053143:Caspase 2 / Q000235:genetics / Q000378:metabolism; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; C524941:MIRN17 microRNA, human; C534451:MIRN20a microRNA, human; C524940:MIRN21 microRNA, human; C532045:MIRN29a microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C490360:CASP2 protein, human; C505520:CASP7 protein, human; C505530:CASP8 protein, human; D053143:Caspase 2; D053179:Caspase 7; D053181:Caspase 8; D003546:Cysteine Endopeptidases
keywords: apoptosis; gene expression; miRNA; oral squamous cell carcinoma; real-time PCR