Zhang Jian-Yu, Shi Ke-Zhi, Liao Xiang-Yu, Li Shi-Jun, Bao Dan, Qian Ying, Li Dao-Jun
The First College of Clinical Medical Science, Three Gorges University & Yichang Central People's Hospital, Yichang, China.
Biomed Res Int. 2021 Jun 19;2021:9922185. doi: 10.1155/2021/9922185. eCollection 2021.
The proteasome has been validated as an anticancer drug target, while the role of a subunit of proteasome, PSMC6, in lung adenocarcinoma (LUAD) has not been fully unveiled. In this study, we observed that both the RNA and protein of PSMC6 were highly upregulated in LUAD compared with the adjacent normal tissues. Moreover, a high PSMC6 expression was associated with poor prognosis. In accordance with this finding, PSMC6 was associated with poor tumor differentiation. Furthermore, the silence of PSMC6 by small interference RNAs (siRNAs) could significantly inhibit cell growth, migration, and invasion in lung cancer cell lines, suggesting that PSMC6 might serve as a promising therapeutic target in LUAD. To further explore the molecular mechanism of PSMC6 in LUAD, we observed that the proteasome subunits, such as PSMD10, PSMD6, PSMD9, PSMD13, PSMB3, PSMB1, PSMA4, PSMC1, PSMC2, PSMD7, and PSMD14, were highly correlated with PSMC6 expression. Based on the gene set enrichment analysis, we observed that these proteasome subunits were involved in the degradation of AXIN protein. The correlation analysis revealed that the positively correlated genes with PSMC6 were highly enriched in WNT signaling-related pathways, demonstrating that the PSMC6 overexpression may activate WNT signaling via degrading the AXIN protein, thereby promoting tumor progression. In summary, we systematically evaluated the differential expression levels and prognostic values of PSMC6 and predicted its biological function in LUAD, which suggested that PSMC6 might act as a promising therapeutic target in LUAD.
蛋白酶体已被确认为一种抗癌药物靶点，而蛋白酶体亚基PSMC6在肺腺癌（LUAD）中的作用尚未完全阐明。在本研究中，我们观察到与相邻正常组织相比，PSMC6的RNA和蛋白质在LUAD中均高度上调。此外，PSMC6高表达与预后不良相关。与此发现一致，PSMC6与肿瘤低分化有关。此外，小干扰RNA（siRNA）沉默PSMC6可显著抑制肺癌细胞系的细胞生长、迁移和侵袭，这表明PSMC6可能是LUAD中有前景的治疗靶点。为了进一步探索PSMC6在LUAD中的分子机制，我们观察到蛋白酶体亚基，如PSMD10、PSMD6、PSMD9、PSMD13、PSMB3、PSMB1、PSMA4、PSMC1、PSMC2、PSMD7和PSMD14，与PSMC6表达高度相关。基于基因集富集分析，我们观察到这些蛋白酶体亚基参与AXIN蛋白的降解。相关性分析显示，与PSMC6呈正相关的基因在WNT信号相关通路中高度富集，表明PSMC6过表达可能通过降解AXIN蛋白激活WNT信号，从而促进肿瘤进展。总之，我们系统地评估了PSMC6的差异表达水平和预后价值，并预测了其在LUAD中的生物学功能，这表明PSMC6可能是LUAD中有前景的治疗靶点。
