BARX2 expression is downregulated by CpG island hypermethylation and is associated with suppressed cell proliferation and invasion of gastric cancer cells.
Oncol Rep
; 43(6): 1805-1818, 2020 06.
Article
en En
| MEDLINE
| ID: mdl-32236603
ABSTRACT
BarHlike homeobox 2 (BARX2), a homeobox gene, is associated with several types of cancers. The present study aimed to determine whether DNA methylation downregulates BARX2 expression and whether BARX2 is associated with suppression of gastric carcinogenesis. BARX2 protein expression in normal and cancerous gastric tissues and various gastric cancer (GC) cell lines was detected using immunohistochemical and western blot assays. BARX2 mRNA levels were detected using both reverse transcriptionpolymerase chain reaction (RTPCR) and quantitative PCR (qPCR). Promoter hypermethylation in GC cells was detected using methylationspecific PCR or bisulfite DNA sequencing PCR. Effects of BARX2 expression on GC cell proliferation, clonal formation, and migration were evaluated after lentivirusBARX2 transfection. The effect of stable BARX2 transfection on tumor formation was assessed in a nude xenograft mouse model. BARX2 was strongly expressed in the normal gastric mucosa, but weakly or not expressed in GC tissues and most GC cell lines. BARX2 expression was negatively correlated with DNMT (a marker for DNA methylation) expression in the gastric tissues. The BARX2 promoter fragment was hypermethylated in the GC cell lines. Overexpression of BARX2 significantly inhibited GC cell proliferation, clonal formation, and migration. Stable BARX2 transfection inhibited tumor formation in xenograft mice, which was correlated with decreased expression of Ecadherin, proliferation markers, and matrix metalloproteinases. In conclusion, BARX2 expression is aberrantly reduced in GC, which is associated with increased DNA methylation of its promoter. BARX2 inhibits GC cell proliferation, migration, and tumor formation, suggesting that BARX2 acts as a tumor suppressor in gastric carcinogenesis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
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Regulación hacia Abajo
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Proteínas de Homeodominio
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Metilación de ADN
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
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Aged
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Aged80
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2020
Tipo del documento:
Article