ARNT-dependent CCR8 reprogrammed LDH isoform expression correlates with poor clinical outcomes of prostate cancer.
Mol Carcinog
; 59(8): 897-907, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32319143
ABSTRACT
Lactate dehydrogenase isozyme (LDH) is a tetramer constituted of two isoforms, LDHA and LDHB, the expression of which is associated with cell metabolism and cancer progression. Our previous study reveals that CC-chemokine ligand-18 (CCL18) is involved in progression of prostate cancer (PCa).This study aims to investigate how CCL18 regulates LDH isoform expression, and therefore, contributes to PCa progression. The data revealed that the expression of LDHA was upregulated and LDHB was downregulated in PCa cells by CCL18 at both messenger RNA and protein levels. The depletion of CCR8 reduced the ability of CCL18 to promote the proliferation, migration, and lactate production of PCa cells. Depletion of a CCR8 regulated transcription factor, ARNT, significantly reduced the expression of LDHA. In addition, The Cancer Genome Atlas dataset analyses revealed a positive correlation between CCR8 and ARNT expression. Two dimension difference gel electrophoresis revealed that the LDHA/LDHB ratio was increased in the prostatic fluid of patients with PCa and PCa tissues. Furthermore, increased LDHA/LDHB ratio was associated with poor clinical outcomes of patients with PCa. Together, our results indicate that the CCR8 pathway programs LDH isoform expression in an ARNT dependent manner and that the ratio of LDHA/LDHB has the potential to serve as biomarkers for PCa diagnosis and prognosis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Biomarcadores de Tumor
/
Regulación Neoplásica de la Expresión Génica
/
Quimiocinas CC
/
Translocador Nuclear del Receptor de Aril Hidrocarburo
/
Receptores CCR8
/
L-Lactato Deshidrogenasa
Tipo de estudio:
Prognostic_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
Mol Carcinog
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2020
Tipo del documento:
Article
País de afiliación:
China