Hsa-Let-7c-3p Inhibits Retinoblastoma Cell Growth and Metastasis and Induces Pyroptosis by Targeting ARHGAP11A

Retinoblastoma (Rb) is a malignant intraocular tumor commonly seen in infants and young children, whose exact cause is unknown. This study aimed to investigate the molecular mechanisms affecting Rb progression. Hsa-let-7c-3p and ARHGAP11A were screened by bioinformatics. RT-qPCR and western blotting were used to detect the expression of hsa-let-7c-3p and ARHGAP11A, and their targeting relationship was examined by a dual luciferase reporter assay. Transwell or CCK-8 was used for cell invasion or viability evaluation. Pyroptosis was evaluated by detecting caspase-1 activity, cleaved GSDMD expression, and IL-1β/IL-18 secretion. The receiver operating characteristic (ROC) curve and binary logistic regression model were used to evaluate the diagnostic value of hsa-let-7c-3p/ARHGAP11A in Rb. Hsa-let-7c-3p was downregulated in Rb cells, and it inhibited ARHGAP11A expression by binding to its mRNA. Overexpression of ARHGAP11A intensified the malignant phenotypes of Rb cells and reversed the growth/invasion inhibition and pyroptosis promotion induced by hsa-let-7c-3p upregulation. Hsa-let-7c-3p and ARHGAP11A were the factors influencing Rb, and their combination showed higher accuracy in diagnosing Rb (AUC = 0.905) compared with single-factor prediction. In conclusion, Hsa-let-7c-3p suppressed Rb cell proliferation/invasion and induced pyroptosis by negatively regulating ARHGAP11A. They are potential biomarkers of Rb.