Guangxi Medical University, Nanning, China.
Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
FEBS Open Bio. 2022 Nov;12(11):2025-2041. doi: 10.1002/2211-5463.13479. Epub 2022 Sep 22.
Aberrant expression of members of the proteasome subunit beta (PSMB) family (including PSMB2, PSMB4, PSMB7 and PSMB8) has been reported in hepatocellular carcinoma (HCC). However the role of PSMB5 in HCC is unclear. To address this issue, we examined the expression of PSMB5 in HCC tissues using the The Cancer Genome Atlas, International Cancer Genome Consortium and Gene Expression Omnibus databases. A quantitative real-time PCR and immunohistochemistry were performed to validate the expression of PSMB5 in HCC. The survival mutation status and immune cell infiltration of PSMB5 were also evaluated in HCC. We then examined the effect of knocking down PSMB5 expression through RNA interference in the HCC cell line Huh7. High expression of PSMB5 was observed in HCC tissues and was associated with poor prognosis. PSMB5 expression and clinical characteristics were then incorporated to build a prognostic nomogram. We observed that PSMB5 expression was closely related to the abundance of B cells, CD4 T cells, CD8 T cells, dendritic cell macrophages and neutrophils. Moreover silencing of PSMB5 in Huh7 significantly suppressed cell proliferation and migration at the same time as increasing apoptosis. Inhibition of the phosphatidylinositol-3-kinase/Akt/mechanistic target of rapamycin pathway was observed after PSMB5 downregulation in Huh7 cells. Our findings suggest that PSMB5 may promote the proliferation of HCC cells by inactivating the phosphatidylinositol-3-kinase/Akt/mechanistic target of rapamycin signaling pathway and thus PSMB5 may have potential as a biomarker for diagnosis and prognosis of HCC.
蛋白酶体亚基β（PSMB）家族成员（包括 PSMB2、PSMB4、PSMB7 和 PSMB8）的异常表达已在肝细胞癌（HCC）中报道。然而，PSMB5 在 HCC 中的作用尚不清楚。为了解决这个问题，我们使用癌症基因组图谱、国际癌症基因组联盟和基因表达综合数据库检查了 HCC 组织中 PSMB5 的表达。通过定量实时 PCR 和免疫组织化学验证了 HCC 中 PSMB5 的表达。还评估了 HCC 中 PSMB5 的生存突变状态和免疫细胞浸润。然后，我们通过 RNA 干扰在 HCC 细胞系 Huh7 中检查了敲低 PSMB5 表达的效果。在 HCC 组织中观察到 PSMB5 的高表达与预后不良相关。然后将 PSMB5 表达与临床特征结合起来构建预后列线图。我们观察到 PSMB5 表达与 B 细胞、CD4 T 细胞、CD8 T 细胞、树突状细胞巨噬细胞和中性粒细胞的丰度密切相关。此外，在 Huh7 中沉默 PSMB5 同时显著抑制细胞增殖和迁移，同时增加细胞凋亡。在 Huh7 细胞中下调 PSMB5 后观察到磷脂酰肌醇-3-激酶/Akt/雷帕霉素靶蛋白信号通路被抑制。我们的研究结果表明，PSMB5 可能通过失活磷脂酰肌醇-3-激酶/Akt/雷帕霉素靶蛋白信号通路促进 HCC 细胞的增殖，因此 PSMB5 可能具有作为 HCC 诊断和预后的生物标志物的潜力。
