He Zirui, Yang Xiao, Huang Ling, Zhou Leqi, Zhang Sen, Sun Jing, Zheng Minhua, Ma Junjun, Feng Bo, Zang Lu
Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Cell Dev Biol. 2021 Jul 16;9:657917. doi: 10.3389/fcell.2021.657917. eCollection 2021.
We designed the present study to access the roles and mechanisms of PSMC5 in colorectal cancer (CRC). Transcriptomic and clinical data from public datasets and our center were retrospectively analyzed. Functional assays were performed to investigate the effects of PSMC5 on CRC cells. The results showed that PSMC5 was significantly higher in cancer than normal tissues. Moreover, patients with higher expression of PSMC5 showed poorer prognosis. Silencing of PSMC5 dramatically suppressed the proliferation and invasion of CRC cells, while overexpression led to the opposite. In addition, we screened downstream targets and found that PSMC5 regulates multiple pathways including epithelial-mesenchymal transition, hypoxia, and immune response. Consistently, we found that PSMC5 was negatively correlated with levels of CD8 + T cells and B cells while promoting infiltration of macrophages and neutrophils. Collectively, these findings suggested that PSMC5 was a promising biomarker and target for immune therapy for CRC.
我们设计了本研究以探讨PSMC5在结直肠癌(CRC)中的作用和机制。对来自公共数据集和我们中心的转录组学及临床数据进行了回顾性分析。进行了功能试验以研究PSMC5对CRC细胞的影响。结果显示,PSMC5在癌组织中显著高于正常组织。此外,PSMC5表达较高的患者预后较差。沉默PSMC5可显著抑制CRC细胞的增殖和侵袭,而过表达则导致相反结果。此外,我们筛选了下游靶点,发现PSMC5可调节多种途径,包括上皮-间质转化、缺氧和免疫反应。一致地,我们发现PSMC5与CD8 + T细胞和B细胞水平呈负相关,同时促进巨噬细胞和中性粒细胞的浸润。总体而言,这些发现表明PSMC5是CRC免疫治疗的一个有前景的生物标志物和靶点。