State Key Laboratory of Biotherapy and Department of Pharmacy, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, P.R. China.
College of Environmental Sciences and Engineering, Peking University, Beijing 100871, P.R. China.
Int J Oncol. 2021 Dec;59(6). doi: 10.3892/ijo.2021.5286. Epub 2021 Nov 15.
Previous studies have showed that proteasome activator complex subunit 2 (PSME2) may play a role in some types of cancer. However, the involvement of PSME2 in clear cell renal cell carcinoma (ccRCC) remains unknown. The aim of the present study was to assess the poorly understood function of PSME2 expression in renal carcinoma. Using bioinformatics analysis, PSME2 mRNA expression profiles were investigated, along with its potential prognostic value and its functional enrichment. Signaling pathways and putative hub genes associated with PSME2 in ccRCC were identified. Based on the bioinformatics analysis results, immunohistochemistry of human ccRCC samples and renal carcinoma cell lines (CAKI‑1 and 786‑O) transfected with short interfering RNA targeting PSME2 were analyzed using western blot analysis, reverse transcription‑quantitative PCR, immunofluorescence, and Cell Counting Kit‑8, Transwell and transmission electron microscope assays. The results showed that when PSME2 expression was knocked down, the invasive abilities of the tumor cell lines were reduced, while autophagy was enhanced. The present study demonstrated that PSME2 was associated with the invasion ability of ccRCC cell lines by inhibiting BNIP3‑mediated autophagy. In summary, PSME2 could be used as a prognostic factor and a promising therapeutic target in ccRCC.
先前的研究表明,蛋白酶体激活剂复合物亚基 2(PSME2)可能在某些类型的癌症中发挥作用。然而,PSME2 在透明细胞肾细胞癌(ccRCC)中的作用尚不清楚。本研究旨在评估 PSME2 表达在肾癌中未被充分了解的功能。本研究通过生物信息学分析,研究了 PSME2 mRNA 表达谱及其潜在的预后价值和功能富集。鉴定了与 ccRCC 中 PSME2 相关的信号通路和潜在的枢纽基因。基于生物信息学分析结果,采用 Western blot 分析、逆转录-定量 PCR、免疫荧光和细胞计数试剂盒-8、Transwell 和透射电子显微镜检测分析了针对 PSME2 的短发夹 RNA 转染的人 ccRCC 样本和肾癌细胞系(CAKI-1 和 786-O)中的 PSME2 免疫组织化学。结果表明,当 PSME2 表达被敲低时,肿瘤细胞系的侵袭能力降低,而自噬增强。本研究表明,PSME2 通过抑制 BNIP3 介导的自噬与 ccRCC 细胞系的侵袭能力相关。综上所述,PSME2 可作为 ccRCC 的预后因素和有前途的治疗靶点。