SP1-activated USP27X-AS1 promotes hepatocellular carcinoma progression via USP7-mediated AKT stabilisation

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.

AKT; USP27X-AS1; USP7; hepatocellular carcinoma; ubiquitination.