KIF11 Regulates the Tumor Microenvironment Through the NLRP3-caspase1-Pyroptosis Pathway to Promote Renal Cell Carcinoma Cell Growth

This article aims to explore the effect of KIF11 (kinesin family member 11) on pyroptosis ofRCC (renal cell carcinoma) cells and its potential mechanisms. ACHN cells were divided into seven groups: si-KIF11-NC group, si-KIF11 group, si-KIF11+Ac-YVAD-CMK group, si-NLRP3 (NOD-like receptor thermal protein domain associated protein 3)-NC group, si-NLRP3 group, si-NLRP3+si-KIF11 group, and si-KIF11+MCC950group. RT-qPCR (reverse transcription quantitative polymerase chain reaction) and Western blot analysis of theexpression of KIF11, NLRP3, and pyroptosis-related genes or proteins in cells; ELISA (enzyme-linked immunosorbent assay) kit detection of cell caspase-1 activity and level of IL-1β (interleukin-1β) and IL-18; flow cytometrywas used to detect the rate of pyroptosis in cells; the colony formation assay and the cell scratch assay were used todetect cell proliferation and migration, respectively. The results showed that, compared with HK-2 cells, RCC cellsexhibited increased mRNA and protein expression level of KIF11 (P<0.05), alongside significantly reduced proteinexpression level of caspase-1 and NLRP3 (P<0.05). Compared with the si-KIF11-NC group, the si-KIF11 groupshowed significant increases in caspase-1 activity, IL-1β level, IL-18 level, cleaved caspase-1 protein level, NGSDMD protein level, IL-1β protein level, IL-18 protein level, and the rate of pyroptosis (P<0.05). Compared withthe si-KIF11 group, the si-KIF11+Ac-YVAD-CMK group showed significantly reduced in caspase-1 activity, IL1β level, IL-18 level, cleaved caspase-1 protein level, N-GSDMD protein level, IL-1β protein level, IL-18 proteinlevel, and the rate of pyroptosis (P<0.05). Compared with the si-KIF11 group, the si-NLRP3+si-KIF11 group andthe si-KIF11+MCC950 group displayed significantly lower protein expression level of NLRP3, cleaved caspase-1,N-GSDMD, IL-1β, and IL-18, as well as a significantly reduced rate of pyroptosis in ACHN cells (P<0.05). Compared with the si-KIF11-NC group, the si-KIF11 group exhibited a significant decrease in both the number of colonies formed and the migration rate of ACHN cells (P<0.05). Compared with the si-KIF11 group, the si-KIF11+AcYVAD-CMK group, the si-NLRP3+si-KIF11 group, and the si-KIF11+MCC950 group all showed significantincreases in colony formation and migration rates of ACHN cells (P<0.05). Therefore, KIF11 knockout may inhibitthe proliferation and migration of RCC cells by inducing pyroptosis regulated by the NLRP3 inflammasome.

CSTR: 32200.14.cjcb.2026.06.0006