Effects of Proteasome 20S Subunit Beta 8 on Proliferation,Migration,and Invasion of Clear Cell Renal Cell Carcinoma Cells via Mitogen-Activated Protein Kinase Kinase/Extracellular Signal-Regulated Kinase Signaling Pathway
10.3881/j.issn.1000-503X.16003
- VernacularTitle:蛋白酶体20S亚基β8调控丝裂原活化蛋白激酶激酶/细胞外信号调节激酶通路对肾透明细胞癌细胞增殖、迁移和侵袭的影响
- Author:
Yufei HAO
1
;
Yu SHI
;
Jinxiu ZHENG
;
Xueting ZHAO
;
Shenglu LIU
;
Lijun YANG
Author Information
1. 山西医科大学基础医学院药理学教研室,太原 030001
- Keywords:
clear cell renal cell carcinoma;
proteasome 20S subunit beta 8;
mitogen-activated protein kinase kinase/extracel-lular signal-regulated kinase signaling pathway
- From:
Acta Academiae Medicinae Sinicae
2024;46(5):641-652
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of proteasome 20S subunit beta 8(PSMB8)on the prolif-eration,migration,and invasion of clear cell renal cell carcinoma(ccRCC)cells and whether PSMB8 promotes tumor progression by activating the mitogen-activated protein kinase kinase(MEK)/extracellular signal-regula-ted kinase(ERK)signaling pathway.Methods The Cancer Genome Atlas was employed to analyze the mRNA levels of PSMB8 in ccRCC and normal tissue,and the expression levels of PSMB8 in ccRCC tissue and cells were determined by real-time quantitative PCR,Western blotting,and immunohistochemistry.Furthermore,the cell lines with stable overexpression and knockdown of PSMB8 were constructed.The CCK-8 assay and colony forma-tion assay were employed to examine the cell proliferation,and the wound healing assay and Transwell assay were employed to examine the invasion and migration of cells.Kyoto Encyclopedia of Genes and Genomes pathway enrich-ment was performed to analyze the co-expressed genes of PSMB8.Western blotting was used to measure the phospho-rylation levels of the proteins in the MEK/ERK signaling pathway.Finally,the rescue experiment was carried out with the ERK agonist C16-PAF.Results Compared with the normal tissue,the ccRCC tissue showed up-regulated mRNA and protein levels of PSMB8(both P＜0.001),which were associated with the TNM stage of patients with ccRCC(P＜0.001).Compared with the negative control group,overexpression of PSMB8 promoted the prolifera-tion(P=0.021,P=0.039),migration and invasion(all P＜0.001)of 786-O and ACHN cells,and the knock-down of PSMB8 inhibited the proliferation(P=0.022,P=0.005),migration and invasion(all P＜0.001)of 786-O and ACHN cells.The pathway enrichment analysis of co-expressed genes of PSMB8 predicted the mitogen-ac-tivated protein kinase signaling pathway(P＜0.001).After the knockdown of PSMB8,786-O and ACHN cells showed lowered phosphorylation levels of MEK1/2(P=0.017,P=0.016)and ERK1/2(P=0.010,P=0.040)and down-regulated transcription levels of ERK downstream factors c-Myc(P=0.043,P=0.038),c-Fos(P=0.025,P=0.008),and CyclinD1(P=0.006,P=0.047).Compared with the ERK agonist C16-PAF group,the PSMB8 knockdown+C16-PAF group showed inhibited proliferation(P=0.003,P=0.002),migration and invasion(all P＜0.001)of 786-O and ACHN cells.Conclusion PSMB8 may promote the proliferation,migration,and invasion of ccRCC cells by activating the MEK/ERK signaling pathway.
