肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一。 STAM 结合蛋白样 1 (STAMBPL1) 是 COP9 信号体亚基 5/丝氨酸蛋白酶 27/蛋白酶体 26S 亚基非 ATP 酶 7 (JAMM) 家族的关键成员，与肿瘤发生密切相关。本工作对GSE101728和GSE84402芯片的数据进行了分析，并选择STAMBPL1作为目标因子。本研究旨在揭示 STAMBPL1 在 HCC 中的潜在功能。临床结果显示，STAMBPL1在HCC患者的肿瘤组织中显着升高，其表达与肿瘤大小和TNM分期密切相关。此外，分别使用携带编码STAMBPL1 mRNA的cDNA或靶向STAMBPL1的shRNA的慢病毒建立STAMBPL1过表达的Hep3B2.1-7细胞系或STAMBPL1沉默的SNU-182细胞系。 STAMBPL1 过表达的细胞在体外和体内表现出明显的增殖增强。外源表达 STAMBPL1 增加了 S 期细胞的百分比，并上调了 CyclinD1 和 Survivin 的表达。正如预期的那样，STAMBPL1 敲低表现出完全相反的效果，导致体外和体内致瘤性受损。从机制上讲，STAMBPL1激活Wnt/β-catenin通路并增加下游促癌基因的表达。有趣的是，我们发现 STAMBPL1 受到甾醇调节元件结合蛋白 1 (SREBP1) 的转录调节，甾醇调节元件结合蛋白 1 (SREBP1) 是一种脂质代谢调节剂，荧光素酶报告基因和染色质免疫沉淀 (Ch-IP) 测定证明了这一点。值得注意的是，STAMBPL1 过度表达增加了 HCC 细胞和异种移植肿瘤中的脂质积累。我们的研究结果总体表明 STAMBPL1 在 HCC 细胞的致瘤性中发挥着至关重要的作用。 Wnt/β-连环蛋白和脂质代谢的调节可能有助于其促癌作用。 STAMBPL1 可能作为 HCC 的治疗靶点。© 2024 Wiley periodicals LLC。

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. STAM binding protein-like 1 (STAMBPL1), a key member of the COP9 signalosome subunit 5/serine protease 27/proteasome 26S subunit non-ATPase 7 (JAMM) family, is closely associated with tumor development. In this work, data from GSE101728 and GSE84402 chips were analyzed, and STAMBPL1 was selected as the target factor. This study aimed to reveal the potential function of STAMBPL1 in HCC. Clinical results showed that STAMBPL1 was significantly increased in tumor tissues of HCC patients, and its expression was strongly associated with tumor size and TNM stage. Furthermore, STAMBPL1-overexpressed Hep3B2.1-7 cell line or STAMBPL1-silenced SNU-182 cell line were established using lentivirus carrying cDNA encoding STAMBPL1 mRNA or shRNA targeting STAMBPL1, respectively. STAMBPL1-overexpressed cells exhibited a pronounced enhancement of proliferation in vitro and in vivo. Exogenous expression of STAMBPL1 increased the percentage of cells in the S phase and upregulated the expressions of CyclinD1 and Survivin. As expected, STAMBPL1 knockdown exhibited completely opposite effects, resulting in impaired tumorigenicity in vitro and in vivo. Mechanistically, STAMBPL1 activated Wnt/β-catenin pathway and increased the expression of downstream cancer-promoting genes. Interestingly, we found that STAMBPL1 was transcriptionally regulated by sterol regulatory element-binding protein 1 (SREBP1), a modulator of lipid metabolism, as evidenced by luciferase reporter and chromatin-immunoprecipitation (Ch-IP) assays. Notably, STAMBPL1 overexpression increased lipid accumulation in HCC cells and xenograft tumors. Totally our findings suggest that STAMBPL1 plays a vital role in the tumorigenicity of HCC cells. Modulation of Wnt/β-catenin and lipid metabolism may contribute to its pro-cancer effects. STAMBPL1 may serve as a therapeutic target of HCC.© 2024 Wiley Periodicals LLC.