Cleavage and polyadenylation specific factor 4 promotes colon cancer progression by transcriptionally activating hTERT.
Biochim Biophys Acta Mol Cell Res
; 1866(10): 1533-1543, 2019 10.
Article
en En
| MEDLINE
| ID: mdl-31301362
ABSTRACT
CPSF4 was identified as a crucial tumorigenic factor in lung cancer development. However, its precise function and the underlying molecular mechanisms in colon cancer progression remain completely unknown. Here, we demonstrate CPSF4 was highly expressed in human colon cancer cells and tissues. Its knockdown inhibited colorectal cancer progression in vitro, including cell proliferation, migration, invasion and stemness maintenance. In contrast, the ectopic overexpression of CPSF4 had the opposite effects in vitro and in vivo. Further mechanistic studies demonstrated that CPSF4 facilitated colorectal tumorigenesis and development partially through transcriptionally regulating hTERT expression by cooperating with NF-kB1 and co-anchoring at hTERT promoter -321 to -234 fragment. In addition, clinical samples analysis indicated that CPSF4 expression was positively correlated with hTERT, and the simultaneously high expression of CPSF4 and hTERT predicted poor patient outcome. Overall, our findings established CPSF4 as a pro-tumorigenic factor in colorectal cancer progression, and suggested that targeting CPSF4-hTERT axis may represent a promising therapeutic strategy in colon cancer treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias del Colon
/
Progresión de la Enfermedad
/
Predisposición Genética a la Enfermedad
/
Factores de Escisión y Poliadenilación de ARNm
/
Factor de Especificidad de Desdoblamiento y Poliadenilación
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Biochim Biophys Acta Mol Cell Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
China