有令人信服的证据表明，长链非编码RNA（lncRNA）在肝细胞肝癌（HCC）的发展中起着重要作用。本研究的目的是调查lncRNA XXYLT1 antisense-2（XXYLT1-AS2）在HCC进展中的作用。采用实时荧光定量PCR来评估HCC患者和正常患者血浆中XXYLT1-AS2的水平。监测细胞增殖、凋亡、迁移和侵袭，并建立肿瘤异种移植模型，通过体外和体内的增减功能研究来研究XXYLT1-AS2的生物学功能，使用免疫沉淀、泛素化实验和Western blot检测自噬标志物和转录因子EB（TFEB）的表达。使用自噬抑制剂3-甲基腺嘌呤（3MA）和蛋白酶体抑制剂MG132来验证自噬在HCC进展中的作用以及XXYLT1-AS2对TFEB泛素化的影响。 在本研究中，我们发现lncRNA XXYLT1-AS2在HCC血浆中高表达，并在体内促进肿瘤生长。在功能研究中，发现XXYLT1-AS2的静默表达抑制了HCC的增殖、迁移、侵袭并激活了HCC细胞的自噬作用，而这些作用都被自噬抑制剂3MA所减弱。从机制上讲，XXYLT1-AS2通过促进TFEB的泛素化降解，降低了TFEB的蛋白水平。XXYLT1-AS2通过抑制自噬，通过促进TFEB的降解在HCC进展中发挥了致癌作用，因此可能成为HCC治疗的新靶点。 © 2023年。作者得到了Federación de Sociedades Españolas de Oncología（FESEO）的独家许可。

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.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.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.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.© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).