Cleavage and polyadenylation-specific factor 3 induces cell cycle arrest via PI3K/Akt/GSK-3ß signaling pathways and predicts a negative prognosis in hepatocellular carcinoma.
Biomark Med
; 15(5): 347-358, 2021 04.
Article
in En
| MEDLINE
| ID: mdl-33666519
ABSTRACT
Background:
Recent studies have shown that cleavage and polyadenylation-specific factor 3 (CPSF3) is a promising antitumor therapeutic target, but its potential role in hepatocellular carcinoma (HCC) has not been reported. Materials &methods:
We explored the expression pattern of CPSF3 in HCC through bioinformatics analysis, quantitative polymerase chain reaction (qPCR) and western blot. The potential role of CPSF3 as a biomarker for HCC was evaluated by Kaplan-Meier analysis. Next, changes in HCC cell lines in the CPSF3 knockdown model group and the control group were assessed by Cell Counting Kit-8, clonal formation, flow cytometry and EdU staining. Western blot detected changes in protein levels of the PI3K/Akt/GSK-3ß axis of two HCC cell lines in the knockdown group and the control group.Results:
The results showed that the transcription and protein levels of CPSF3 were significantly higher in HCC tissues than in adjacent normal tissues (p < 0.05). The HCC cohort with increased expression of CPSF3 is associated with advanced stage and differentiation and predicts poorer prognosis (p < 0.05). CPSF3 knockdown significantly inhibited proliferation and clone formation of HepG2 and SMMC-7721 cell lines. Flow cytometry analysis showed G1-S cell cycle arrest in the CPSF3 knockdown group, and the results of EdU staining were consistent with this. Compared with the control group, p-Akt and cyclin D1 were decreased, and GSK-3ß was increased in the knockdown group.Conclusion:
CPSF3 may be a potential diagnostic biomarker and candidate therapeutic target for HCC.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Regulation, Neoplastic
/
Carcinoma, Hepatocellular
/
Phosphatidylinositol 3-Kinases
/
Cleavage And Polyadenylation Specificity Factor
/
Proto-Oncogene Proteins c-akt
/
Glycogen Synthase Kinase 3 beta
/
Liver Neoplasms
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Biomark Med
Journal subject:
BIOQUIMICA
/
MEDICINA
Year:
2021
Document type:
Article
Affiliation country: