Heat-Shock Protein 4 (HSP-4) Promote Renal Cell Carcinoma Metastasis via Negatively Regulating KLF6

Abstract

This project investigates the role and mechanisms of HSP4 and KLF6 in renal clear cell carcinoma (RCC) metastasis at molecular, cellular, and clinical levels. HSP4 expression was analyzed in RCC tissue specimens, cell lines, and its relationship with clinicopathological indicators. RCC cell lines with elevated HSP4 were transfected with HSP4 knockdown vectors, and the impact on cell invasion was assessed. The interaction between HSP4 and KLF6 was confirmed through luciferase assays and cell experiments. HSP4 expression was significantly higher in RCC tissues and cell lines compared to normal samples. Higher HSP4 levels were associated with increased metastasis incidence in RCC patients. HSP4 knockdown suppressed cell migration. Luciferase assays showed that HSP4 targets KLF6. KLF6 mRNA levels were inversely correlated with HSP4 in RCC tissues. Knockdown of HSP4 increased KLF6 levels, and vice versa, indicating a negative correlation. Inhibition of KLF6 counteracted the inhibitory effect of HSP4 knockdown on RCC cell functions. In conclusion, elevated HSP4 expression is linked to lymph node and distant metastasis in RCC patients. HSP4 likely promotes RCC progression by negatively regulating KLF6, offering insights into RCC-specific biomarkers and its pathogenesis.