LncRNA XXYLT1-AS2 promotes tumor progression via autophagy inhibition through ubiquitinated degradation of TFEB in hepatocellular carcinoma

• Xuejie Li ^[1] ; Yuqin Wu ^[2] ; Pingfeng Wang ^[1] ; Ying Li ^[3] ; Jiangxue Gu ^[1] ; Yuan Zhang ^[1] ; Shirong Yan ^[1] ; Pei Hu ^[1]
  1. [1] Hubei University of Medicine

     Hubei University of Medicine

     China

     
  2. [2] Central Operating Room, Taihe Hospital, Hubei, People’s Republic of China
  3. [3] Blood Transfusion Department, Taihe Hospital, Hubei, People’s Republic of China

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 26, Nº. 3, 2024, págs. 698-708
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Purpose There is compelling evidence that long-stranded non-coding RNAs (lncRNAs) play an important role in the progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of lncRNA XXYLT1 antisense-2 (XXYLT1-AS2) in HCC progression.

    Methods Real-time PCR was used to assess the levels of XXYLT1-AS2 in plasma from HCC and normal patients. Cell proliferation, apoptosis, migration, and invasion were monitored, and tumor xenografts were established to investigate the biological functions of XXYLT1-AS2 by gain-of-function and loss-of-function studies in vitro and in vivo, the expression of autophagy biomarkers and transcriptional factor EB (TFEB) was examined by immunoprecipitation, ubiquitination assays, and western blotting. Autophagy inhibitor, 3-methyladenine (3MA), and proteasome inhibitor, MG132, were used to verify the role of autophagy in HCC progression and the effect of XXYLT1-AS2 on TFEB ubiquitination, respectively.

    Results In this study, we identified that lncRNA XXYLT1-AS2 is highly expressed in HCC plasma and promotes tumor growth in vivo. In functional studies, it was found that silent expression of XXYLT1-AS2 inhibited HCC proliferation, migration, invasion, and activated autophagy of HCC cells, which were attenuated by autophagy inhibitor, 3MA. Mechanistically, XXYLT1-AS2 decreased the protein level of TFEB through promoting its degradation by ubiquitin proteasome pathway.

    Conclusion XXYLT1-AS2 plays an oncogenic role in HCC progression through inhibition of autophagy via promoting the degradation of TFEB, and thus could be a novel target for HCC treatment.