Legumain affects the PI3K/AKT tumor progression pathway in retinoblastoma

Known as a common malignant tumor among children, retinoblastoma (RB) is highly malignant and has poor prognosis, damages children???s vision and degrades quality of life. To identify a potential molecular mechanism of RB, we conducted this study on legumain (LGMN), which is highly expressed in multiple tumors. In this study, we found that LGMN was significantly upregulated in RB cells and was positively expressed in RB tissues. We confirmed that LGMN overexpression (LGMN-OE) can promote RB cell proliferation and inhibit cell apoptosis through CCK8 experiments and flow cytometry. In addition, real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot results showed that LGMN-OE could regulate the expression of epithelialmesenchymal transformation-related genes and proteins, related to tumor invasion and metastasis. Moreover, after LGMN knock down, the result was the opposite., RNA sequence analysis revealed 1159 differentially expressed genes between LGMN-OE and the negative control (NCOE), of which 564 were upregulated and 595 were downregulated. The first 10 genes were verified by RT-qPCR based on P value and fold change. Interestingly, we found that LGMN could regulate the expression of recoverin (RCVRN)through a gene responsible for cancer-related retinopathy. We also screened and verified that LGMN partially activated the PI3K/AKT pathway in RB. Furthermore, we evaluated the effect of legumain inhibitors (e.g., esomeprazole) on RB, and the results suggest that esomeprazole may provide a reference for the clinical adjuvant treatment of RB. In conclusion, legumain can serve as an attractive target for RB therapy and hopefully provide new insights and ideas for the development of targeted drugs and precise personalized clinical therapy.

Automated summary

This study identified legumain as a potential molecular mechanism in retinoblastoma (RB). Legumain was found to be upregulated in RB cells and positively expressed in RB tissues. Legumain overexpression promoted RB cell proliferation and inhibited cell apoptosis. It also regulated the expression of genes and proteins related to tumor invasion and metastasis. RNA sequence analysis revealed differentially expressed genes between legumain overexpression and negative control groups. Legumain was found to partially activate the PI3K/AKT pathway in RB. Legumain inhibitors might provide a reference for clinical adjuvant treatment of RB. Overall, legumain can serve as a target for RB therapy and contribute to the development of targeted drugs and personalized clinical therapy.