HSP90AA1 is a chaperone protein involved in various biological processes, including inflammation and cancer. HSP90AA1 is highly expressed in lung adenocarcinoma (LUAD), but its exact function remains unclear. Here, prognostic analysis of survival data from the TCGA database showed that HSP90AA1 expression is associated with clinicopathological staging. The overall survival (OS) and disease-specific survival (DSS) were significantly higher in the low-expression group of HSP90AA1 compared to the high-expression group. Furthermore, CancerSEA functional similarity analysis revealed that HSP90AA1 is involved in multiple cellular functions, including cell cycle stimulation, DNA damage response, invasion, and proliferation. Analysis of immune scores and immune cell infiltration using the ESTIMATE and TIMER databases showed that high levels of HSP90AA1 were associated with decreased infiltration of CD8+ T cells and plasmacytoid dendritic cells (pDCs), while infiltration of Th2 cells and helper T cells was increased. In vitro experiments further confirmed that knockdown of HSP90AA1 expression significantly inhibited the proliferation of H1299 cells. These findings suggest that silencing HSP90AA1 expression or using HSP90AA1 inhibitors could effectively improve the treatment of LUAD. Targeting HSP90AA1 may be an effective strategy for treating LUAD.
Compared to the control group, the proliferation of HSP90AA1-knockdown H1299 cells was inhibited (Figure 1C). To confirm the reason for the inhibited cell proliferation, researchers used PI staining to detect the cell cycle of H1299 cells. The results showed that, compared to the control group, the number of cells in the G1 phase increased, while the number of cells in the S and G2/M phases decreased in HSP90AA1-knockdown cells (Figure 1D-G). This indicates that the absence of HSP90AA1 leads to H1299 cell cycle arrest in the G1 phase. Furthermore, Western blot experiments confirmed that knocking down HSP90AA1 effectively downregulated the expression of cell cycle-related proteins CCNB1 and CCND1 (Figure 1H, I). These findings suggest that HSP90AA1 may regulate the cell cycle by modulating these specific proteins.
Figure 1. HSP90AA1 is crucial for the proliferation of LUAD cells. (Xiang S, et al., 2025)