In vitro and in silico validation of CA3 and FHL1 downregulation in oral cancer

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dc.citation.volume18
dc.contributor.authorPereira, Claudia Maria
dc.contributor.authorde Carvalho, Ana Carolina [UNIFESP]
dc.contributor.authorda Silva, Felipe Rodrigues
dc.contributor.authorMelendez, Matias Eliseo
dc.contributor.authorLessa, Roberta Cardim
dc.contributor.authorAndrade, Valeria Cristina C. [UNIFESP]
dc.contributor.authorKowalski, Luiz Paulo
dc.contributor.authorVettore, Andre L. [UNIFESP]
dc.contributor.authorCarvalho, Andre Lopes
dc.coverageLondon
dc.date.accessioned2020-07-08T13:09:40Z
dc.date.available2020-07-08T13:09:40Z
dc.date.issued2018
dc.description.abstractBackground: Aberrant methylation is a frequent event in oral cancer. Methods: In order to better characterize these alterations, a search for genes downregulated by aberrant methylation in oral squamous cell carcinoma (OSCC) was conducted through the mining of ORESTES dataset. Findings were further validated in OSCC cell lines and patients' samples and confirmed using TCGA data. Differentially expressed genes were identified in ORESTES libraries and validated in vitro using RT-PCR in HNSCC cell-lines and OSCC tumor samples. Further confirmation of these results was performed using mRNA expression and methylation data from The Cancer Genome Atlas (TCGA) data. Results: From the set of genes selected for validation, CA3 and FHL1 were downregulated in 60% (12/20) and 75% (15/20) of OSCC samples, respectively, and in HNSCC cell lines. The treatment of cell lines JHU-13 and FaDu with the demethylating agent 5'-aza-dC was efficient in restoring CA3 and FHL1 expression. TCGA expression and methylation data on OSCC confirms the downregulation of these genes in OSCC samples and also suggests that expression of CA3 and FHL1 is probably regulated by methylation. The downregulation of CA3 and FHL1 observed in silico was validated in HNSCC cell lines and OSCC samples, showing the feasibility of integrating different datasets to select differentially expressed genes in silico. Conclusions: These results showed that the downregulation of CA3 and FHL1 data observed in the ORESTES libraries was validated in HNSCC cell lines and OSCC samples and in a large cohort of samples from the TCGA database. Moreover, it suggests that expression of CA3 and FHL1 could probably be regulated by methylation having an important role the oral carcinogenesis.en
dc.description.affiliationAC Camargo Canc Hosp, Dept Head & Neck Surg, Sao Paulo, Brazil
dc.description.affiliationLudwig Inst Canc Res, Lab Canc Genet, Sao Paulo, Brazil
dc.description.affiliationBarretos Canc Hosp, Mol Oncol Res Ctr, Barretos, Brazil
dc.description.affiliationEmbrapa Informat Agr, Campinas, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Discipline Hematol & Hemotherapy, UNIFESP, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Sci Biol, UNIFESP, Diadema, Brazil
dc.description.affiliationBarretos Canc Hosp, Dept Head & Neck Surg, Barretos, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Discipline Hematol & Hemotherapy, UNIFESP, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Sci Biol, UNIFESP, Diadema, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Pesquisa (CNPq) |Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipIDCNPq: 476586/2006-2
dc.description.sponsorshipIDFAPESP: 05/02580-8
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1186/s12885-018-4077-3
dc.identifier.citationBmc Cancer. London, v. 18, p. -, 2018.
dc.identifier.doi10.1186/s12885-018-4077-3
dc.identifier.fileWOS000425517300002.pdf
dc.identifier.issn1471-2407
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54124
dc.identifier.wosWOS:000425517300002
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofBmc Cancer
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectOSCCen
dc.subjectGene expressionen
dc.subjectMethylationen
dc.subjectCA3en
dc.subjectFHL1en
dc.titleIn vitro and in silico validation of CA3 and FHL1 downregulation in oral canceren
dc.typeinfo:eu-repo/semantics/article
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