USP14 在肝细胞癌中表达水平较高，通过 HK2/AKT/P62 轴发挥关键作用，促进肝癌细胞的生长。
USP14 exhibits high expression levels in hepatocellular carcinoma and plays a crucial role in promoting the growth of liver cancer cells through the HK2/AKT/P62 axis.
机构信息
Medical College of Nantong University, Nantong, Jiangsu, 226000, China.
Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226000, China.
出版信息
BMC Cancer. 2024 Feb 21;24(1):237. doi: 10.1186/s12885-024-12009-y.
BACKGROUND
Hepatocellular carcinoma (HCC) is a common malignant tumor with strong invasiveness and poor prognosis. Previous studies have demonstrated the significant role of USP14 in various solid tumors. However, the role of USP14 in the regulation of HCC development and progression remains unclear.
METHODS
We discovered through GEO and TCGA databases that USP14 may play an important role in liver cancer. Using bioinformatics analysis based on the Cancer Genome Atlas (TCGA) database, we screened and identified USP14 as highly expressed in liver cancer. We detected the growth and metastasis of HCC cells promoted by USP14 through clone formation, cell counting kit 8 assay, Transwell assay, and flow cytometry. In addition, we detected the impact of USP14 on the downstream protein kinase B (AKT) and epithelial-mesenchymal transition (EMT) pathways using western blotting. The interaction mechanism between USP14 and HK2 was determined using immunofluorescence and coimmunoprecipitation (CO-IP) experiments.
RESULTS
We found that sh-USP14 significantly inhibits the proliferation, invasion, and invasion of liver cancer cells, promoting apoptosis. Further exploration revealed that sh-USP14 significantly inhibited the expression of HK2. Sh-USP14 can significantly inhibit the expression of AKT and EMT signals. Further verification through immunofluorescence and CO-IP experiments revealed that USP14 co-expressed with HK2. Further research has found that USP14 regulates the glycolytic function of liver cancer cells by the deubiquitination of HK2. USP14 regulates the autophagy function of liver cancer cells by regulating the interaction between SQSTM1/P62 and HK2.
CONCLUSIONS
Our results indicate that USP14 plays a crucial role in the carcinogenesis of liver cancer. We also revealed the protein connections between USP14, HK2, and P62 and elucidated the potential mechanisms driving cancer development. The USP14/HK2/P62 axis may be a new therapeutic biomarker for the diagnosis and treatment of HCC.
背景
肝细胞癌（HCC）是一种常见的恶性肿瘤，具有很强的侵袭性和不良预后。先前的研究表明 USP14 在各种实体瘤中发挥着重要作用。然而，USP14 在调节 HCC 发生和发展中的作用尚不清楚。
方法
我们通过 GEO 和 TCGA 数据库发现 USP14 可能在肝癌中发挥重要作用。基于癌症基因组图谱（TCGA）数据库的生物信息学分析，我们筛选并鉴定出 USP14 在肝癌中高表达。我们通过克隆形成、细胞计数试剂盒 8 检测、Transwell 检测和流式细胞术检测 USP14 促进 HCC 细胞的生长和转移。此外，我们通过 Western blot 检测 USP14 对下游蛋白激酶 B（AKT）和上皮-间充质转化（EMT）通路的影响。通过免疫荧光和免疫共沉淀（CO-IP）实验确定 USP14 与 HK2 之间的相互作用机制。
结果
我们发现 sh-USP14 显著抑制肝癌细胞的增殖、侵袭和侵袭，促进细胞凋亡。进一步探索发现，sh-USP14 显著抑制 HK2 的表达。sh-USP14 可显著抑制 AKT 和 EMT 信号的表达。通过免疫荧光和 CO-IP 实验的进一步验证表明，USP14 与 HK2 共表达。进一步研究发现，USP14 通过 HK2 的去泛素化调节肝癌细胞的糖酵解功能。USP14 通过调节 SQSTM1/P62 和 HK2 之间的相互作用调节肝癌细胞的自噬功能。
结论
我们的研究结果表明，USP14 在肝癌的发生发展中起着关键作用。我们还揭示了 USP14、HK2 和 P62 之间的蛋白质联系，并阐明了驱动癌症发展的潜在机制。USP14/HK2/P62 轴可能成为 HCC 诊断和治疗的新治疗生物标志物。
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