Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing 400042, P.R. China.
Mol Med Rep. 2021 Jan;23(1). doi: 10.3892/mmr.2020.11684. Epub 2020 Nov 17.
Constitutive photomorphogenesis 9 signalosome subunit 1 (CSN1) plays an important role in the ubiquitin-proteasome pathway and regulates various cellular processes, such as the cell cycle and DNA repair. The CSN complex consists of eight subunits (CSN1 to CSN8) and regulates the tumorigenesis of a variety of tumor types. However, the exact role of CSN1 in hepatocellular carcinoma (HCC) remains unclear. The present study evaluated the expression and biological effects of CSN1 in HCC tissue samples and cell lines. CSN1 was significantly overexpressed in HCC tissue and cell lines, compared with their normal counterparts. In patients with HCC, elevated CSN1 levels correlated with tumor size, tumor metastasis and tumor stage. Loss‑of‑function assays indicated that CSN1 knockdown inhibited the proliferation and migration HCC cells. In addition, CSN1 promoted the expression of cyclin A2 in a ubiquitination‑independent manner. Lastly, xenograft experiments indicated that CSN1 promoted HCC tumor growth in vivo. The present study suggested that CSN1 inhibition could represent a potential approach for the prevention of HCC progression and metastasis.
组成型光形态建成 9 信号小体亚基 1（CSN1）在泛素-蛋白酶体途径中发挥重要作用，并调节各种细胞过程，如细胞周期和 DNA 修复。CSN 复合物由八个亚基（CSN1 至 CSN8）组成，调节多种肿瘤类型的肿瘤发生。然而，CSN1 在肝细胞癌（HCC）中的确切作用尚不清楚。本研究评估了 CSN1 在 HCC 组织样本和细胞系中的表达和生物学效应。与正常组织相比，CSN1 在 HCC 组织和细胞系中显著过表达。在 HCC 患者中，CSN1 水平升高与肿瘤大小、肿瘤转移和肿瘤分期相关。功能丧失实验表明，CSN1 敲低抑制 HCC 细胞的增殖和迁移。此外，CSN1 以非泛素化依赖的方式促进细胞周期蛋白 A2 的表达。最后，异种移植实验表明 CSN1 促进 HCC 肿瘤在体内生长。本研究表明，CSN1 抑制可能代表预防 HCC 进展和转移的一种潜在方法。
