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

Publisher: Wiley Country of Publication: United States NLM ID: 101597971 Publication Model: Print Cited Medium: Internet ISSN: 2001-1326 (Electronic) Linking ISSN: 20011326 NLM ISO Abbreviation: Clin Transl Med Subsets: MEDLINE

Publication: 2020- : [Hoboken, NJ] : Wiley
Original Publication: Heidelberg : Springer-Verlag

Carcinoma, Hepatocellular*/metabolism ; Liver Neoplasms*/metabolism ; RNA, Long Noncoding*/genetics ; RNA, Long Noncoding*/metabolism; Humans ; Cell Line, Tumor ; Cell Proliferation/genetics ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Ubiquitin-Specific Peptidase 7/genetics

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.
(© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

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81001305 National Natural Science Foundation of China; 81874189 National Natural Science Foundation of China; 82103597 National Natural Science Foundation of China

Keywords: AKT; USP27X-AS1; USP7; hepatocellular carcinoma; ubiquitination

EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
0 (RNA, Long Noncoding)
EC 3.4.19.12 (Ubiquitin-Specific Peptidase 7)
EC 3.4.19.12 (USP7 protein, human)
EC 3.4.19.12 (USP27X protein, human)
0 (SP1 protein, human)

Date Created: 20240127 Date Completed: 20240204 Latest Revision: 20240417

20240418

PMC10819096

10.1002/ctm2.1563

38279869