High glucose may promote the proliferation and metastasis of hepatocellular carcinoma via E2F1/RRBP1 pathway.
Life Sci
; 252: 117656, 2020 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-32289433
AIMS: Diabetes is considered as one of the important risks in the progression of Hepatocellular carcinoma(HCC). Ribosome binding protein 1 (RRBP1), a rough endoplasmic reticulum protein, plays an essential role in diabetes and various cancer. E2F transcription factor 1 (E2F1), an upstream transcription factor of RRBP1, shows promoting tumor progression effect in multifarious cancers. In this research, we tried to identify whether regulating E2F1/RRBP1 pathway could inhibit the proliferation and metastasis of HepG2 cells induced by high glucose. MAIN METHODS: Proteomic, bioinformatics, molecular biology including RT-qPCR and Western blot, cell biology containing Cell Counting Kit-8 (CCK-8), wound healing assay and transwell assay, and biochemistry analyses incorporating Luciferase assay and CHIP assay were used in this study. KEY FINDINGS: High glucose promoted the proliferation and metastasis of HepG2 cells through up-regulating the expression of RRBP1. Bioinformatics analysis predicted that E2F1 might be the transcription factor of RRBP1. Knocking-down of E2F1 down-regulated mRNA and protein expression levels of RRBP1 in HepG2 cells significantly and suppressed the proliferation, migration and invasion of cells remarkably, Reverse effect was observed in cells that E2F1 was overexpressed. Meanwhile, luciferase and CHIP assay determined that E2F1 could bind to the RRBP1 promoter and promote the transcription of RRBP1. Finally, rescue assay verified the important role of RRBP1/E2F1 axis in the process of HepG2 cells proliferation and metastasis. SIGNIFICANCE: All of the above provided possibility to improve the efficiency of HCC complicated with diabetes treatment by regulating the E2F1/RRBP1 pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Portadoras
/
Carcinoma Hepatocelular
/
Factor de Transcripción E2F1
/
Glucosa
/
Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Life Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos