Overexpression of aquaporin-1 plays a vital role in proliferation, apoptosis, and pyroptosis of Wilms' tumor cells

Background: Nephroblastoma, also known as Wilms' tumor (WT), is an embryonic malignant tumor and one of the most common malignant tumors in the abdominal region of children. The exact role and underlying mechanisms of aquaporin-1 (AQP1) in the occurrence and development of nephroblastoma remain unclear.

Methods: After overexpression of AQP1, cell proliferation was assessed using the CCK-8 proliferation assay and EdU staining. Flow cytometry was employed to assess cell apoptosis, and Western blotting (WB) analysis was conducted to validate the expression of relevant protein markers. mRNA sequencing (mRNA-Seq) was performed on WT cells overexpressing AQP1 to predict and characterize the associated mechanisms. Transmission electron microscopy was utilized to observe changes in the ultrastructure of WT cells undergoing apoptosis and pyroptosis following AQP1 overexpression. Functional in vivo validation was conducted through animal experiments.

Results: We validated that overexpression of AQP1 inhibited cell proliferation and promoted cell apoptosis and pyroptosis both in vitro and in vivo. mRNA-Seq analysis of WT cells with AQP1 overexpression suggested that these effects might be mediated through the inhibition of the JAK-STAT signaling pathway. Additionally, we discovered that overexpression of AQP1 activated the classical pyroptosis signaling pathway dependent on caspase-1, thereby promoting pyroptosis in WT.

Conclusion: These findings highlight the important functional role of AQP1 in the pathobiology of nephroblastoma, providing novel insights into the development of this disease. Moreover, these results offer new perspectives on the potential therapeutic targeting of AQP1 as a treatment strategy for nephroblastoma.