LncRNA XLOC_006390 promotes pancreatic carcinogenesis and glutamate metabolism by stabilizing c-Myc.
Cancer Lett
; 469: 419-428, 2020 01 28.
Article
en En
| MEDLINE
| ID: mdl-31734356
ABSTRACT
The role of lncRNAs in the regulation of glutamate metabolism and metabolic reprogramming of pancreatic cancer (PC) during nutrient deprivation is largely unknown. Our study found that alpha-ketoglutarate (aKG) levels were significantly reduced in the absence of XLOC_006390. We subsequently confirmed that the decrease in aKG was mainly due to the downregulation of glutamate dehydrogenase 1 (GDH1) at the mRNA level. Therefore, we first screened transcription factors targeting the GDH1 gene promoter and confirmed that c-Myc regulates GDH1 transcription. c-Myc binds to the promoter of GDH1 and activates its transcription. Downregulation of GDH1 mRNA levels by XLOC_006390 deletion could be rescued by overexpression of c-Myc. Overexpression of XLOC_006390 promoted the protein stability of c-Myc by blocking its ubiquitination. Clinically, XLOC_006390 was positively correlated with the mRNA level of GDH1, and c-Myc positively regulated GDH1 gene expression, which was tightly associated with PC patient prognosis. The dysregulated lncRNA/c-Myc axis increased glutamate metabolism, promoting PC progression to a higher stage. Therefore, XLOC_006390/c-Myc may be a potential target for PC, and its abnormal activation also indicates the progression of PC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Pancreáticas
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Proteínas Proto-Oncogénicas c-myc
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ARN Largo no Codificante
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Glutamato Deshidrogenasa
Tipo de estudio:
Prognostic_studies
Límite:
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:
Cancer Lett
Año:
2020
Tipo del documento:
Article