| Registro completo |
| Provedor de dados: |
BJMBR
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| País: |
Brazil
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| Título: |
Modulation of the prostaglandin-endoperoxide synthase 2 gene expression by variant haplotypes: influence of the 3′-untranslated region
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| Autores: |
Piranda,D.N.
Abreu,R.B.V.
Freitas-Alves,D.R.
de Carvalho,M.A.
Vianna-Jorge,R.
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| Data: |
2018-01-01
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| Ano: |
2018
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| Palavras-chave: |
COX-2
PTGS2
Haplotypes
Gene expression
MCF-7
HEK293FT
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| Resumo: |
The inducible inflammatory enzyme cycloxigenase-2 is up-regulated in cancer, and favors tumor progression. Cycloxigenase-2 is encoded by the prostaglandin-endoperoxide synthase 2 (PTGS2) gene, which presents sequence variations in the promoter region (PR) and in the 3′-untranslated region (3′-UTR). Different PR (rs689465, rs689466, rs20417) and 3′-UTR (rs5275) variants were generated by site-directed mutagenesis, and combined in haplotypes to access expression levels using a reporter system (luciferase) in human cells (MCF-7 and HEK293FT). Luciferase activity did not differ significantly among PTGS2 PR constructs, except for pAAC (containing variant allele rs20417 C), with 40% less activity than pAAG (wild-type sequence) in MCF-7 cells (P<0.01). Despite the lack of individual significant differences, PTGS2 PR constructs enclosing rs689466 G (pAGG and pAGC) showed an approximate two-fold increase in luciferase activity when compared to those containing rs689466 A (pAAG, pGAC, pAAC and pGAG) in both cell lines (P<0.001 for MCF-7 and P=0.03 for HEK293FT). The effect of PTGS2 3′-UTR sequences varied between MCF-7 and HEK293FT: MCF-7 cells showed significant reduction (40–60%) in luciferase activity (at least P<0.01), whereas HEK293FT cells showed more diverse results, with an average 2-fold increase when combined constructs (PR and 3′-UTR) were compared to respective parental PR sequences. The contribution of 3′-UTR variant (rs5275) was not consistent in either cell line. Despite the modulation of the 3′-UTR, with variable effects of rs5275, the enhancing transcriptional effect of rs689466 G was still detectable (P<0.0001 in MCF-7 or P=0.03 in HEK293FT cells).
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| Tipo: |
Info:eu-repo/semantics/article
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| Idioma: |
Inglês
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| Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2018000200602
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| Editor: |
Associação Brasileira de Divulgação Científica
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| Relação: |
10.1590/1414-431x20176546
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| Formato: |
text/html
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| Fonte: |
Brazilian Journal of Medical and Biological Research v.51 n.2 2018
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| Direitos: |
info:eu-repo/semantics/openAccess
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