Epigenetic upregulation and functional role of the mitochondrial aspartate/glutamate carrier isoform 1 in hepatocellular carcinoma.
Biochim Biophys Acta Mol Basis Dis
; 1865(1): 38-47, 2019 01.
Article
en En
| MEDLINE
| ID: mdl-30321589
ABSTRACT
Metabolic reprogramming is a common hallmark of cancer cells. Although some biochemical features have been clarified, there is still much to learn about cancer cell metabolism and its regulation. Aspartate-glutamate carrier isoform 1 (AGC1), encoded by SLC25A12 gene, catalyzes an exchange between intramitochondrial aspartate and cytosolic glutamate plus a proton across the mitochondrial membrane, so supplying aspartate to the cytosol. SLC25A12, expressed in brain, heart, and skeletal muscle, is silenced in normal liver. Here, we demonstrate that SLC25A12 gene is reactivated in hepatocellular carcinoma (HCC) HepG2 cell line through histone acetylation and CREB recruitment. Furthermore, SLC25A12 knockdown by small interfering RNA, impairs HepG2 cell proliferation by inducing cell cycle arrest. AGC1 sustains HCC cell growth by supplying cytosolic aspartate for nucleotide biosynthesis. In addition, SLC25A12-silenced HCC cells show a strong reduction of cell migration. Overall, we have provided evidence for molecular mechanisms controlling SLC25A12 gene expression in liver and pointing to an important role for AGC1 in HCC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación hacia Arriba
/
Ácido Aspártico
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Antiportadores
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Carcinoma Hepatocelular
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Ácido Glutámico
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Isoformas de Proteínas
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Sistemas de Transporte de Aminoácidos Acídicos
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Epigénesis Genética
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Neoplasias Hepáticas
Límite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Año:
2019
Tipo del documento:
Article