Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, People's Republic of China.
Clin Transl Med. 2024 Jan;14(1):e1563. doi: 10.1002/ctm2.1563.
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.
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.
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.
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.
肝细胞癌（HCC）仍然对患者的生存构成重大威胁。新出现的证据强调了长链非编码 RNA（lncRNA）在癌症过程中的关键作用。然而，我们对 lncRNA 在 HCC 中的作用和过程的理解仍然有限。
通过生物信息学分析和 qRT-PCR 相结合，评估 HCC 患者队列中 USP27X-AS1 的表达水平。随后进行了后续的生物学实验，深入研究 USP27X-AS1 的功能方面。还采用了其他分子生物学技术，包括 RNA 下拉和 RNA 免疫沉淀（RIP），以阐明涉及 HCC 中 USP27X-AS1 的潜在机制。最后，进行了 CUT-RUN 测定和其他研究，以确定导致 HCC 中 USP27X-AS1 表达增加的因素。
新型癌基因 USP27X-AS1 的高表达预测 HCC 患者预后不良。进一步的研究证实，USP27X-AS1 通过使 USP7 与 AKT 相互作用来促进 HCC 的增殖和转移，从而降低 AKT 的多泛素化水平并增强 AKT 蛋白稳定性，从而提高 AKT 蛋白稳定性并促进 HCC 的进展。此外，我们还揭示了 SP1 结合 USP27X-AS1 启动子以激活其转录。
新型致癌 lncRNA USP27X-AS1 通过招募 USP7 来去泛素化 AKT 促进 HCC 进展。SP1 转录激活 USP27X-AS1 的表达。这些发现揭示了 HCC，并指出 USP27X-AS1 作为潜在的预测生物标志物和治疗靶点具有恶性肿瘤。
