SP1-activated USP27X-AS1 promotes hepatocellular carcinoma progression via USP7-mediated AKT stabilisation.
Clin Transl Med
; 14(1): e1563, 2024 01.
Article
in En
| MEDLINE
| ID: mdl-38279869
ABSTRACT
BACKGROUND:
Hepatocellular carcinoma (HCC) continues to pose a significant threat to patient survival. Emerging evidence underscores the pivotal involvement of long non-coding RNAs (lncRNAs) in the cancer process. Nevertheless, our understanding of the roles and processes of lncRNAs in HCC remains limited.METHODS:
The expression level of USP27X-AS1 was assessed in an HCC patient cohort through a combination of bioinformatics analysis and qRT-PCR. Subsequent biological experiments were conducted to delve into the functional aspects of USP27X-AS1. Additional molecular biology techniques, including RNA pulldown and RNA immunoprecipitation (RIP), were employed to elucidate the potential mechanisms involving USP27X-AS1 in HCC. Finally, CUT-RUN assay and other investigations were carried out to determine the factors contributing to the heightened expression of USP27X-AS1 in HCC.RESULTS:
High expression of the novel oncogene USP27X-AS1 predicted poor prognosis in HCC patients. Further investigation confirmed that USP27X-AS1 promoted the proliferation and metastasis of HCC by enabling USP7 to interact with AKT, which reduced level of AKT poly-ubiquitylation and enhanced AKT protein stability, which improves protein stabilisation of AKT and promotes the progression of HCC. Moreover, we also revealed that SP1 binds to USP27X-AS1 promoter to activate its transcription.CONCLUSIONS:
Novel oncogenic lncRNA USP27X-AS1 promoted HCC progression via recruiting USP7 to deubiquitinate AKT. SP1 transcriptionally activated USP27X-AS1 expression. These findings shed light on HCC and pointed to USP27X-AS1 as a potential predictive biomarker and treatment target for the malignancy.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Hepatocellular
/
RNA, Long Noncoding
/
Liver Neoplasms
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Clin Transl Med
Year:
2024
Document type:
Article