PRDX1 knockdown promotes erastin-induced ferroptosis and impedes diffuse large B-cell lymphoma development by inhibiting the MAPK/ERK pathway.

AIM

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma and DLBCL cells are highly sensitive to ferroptosis. The purpose of this research was to evaluate the role and molecular mechanism of peroxiredoxin 1 (PRDX1) on ferroptosis in DLBCL.

METHODS

The expression of PRDX1 in DLBCL tissues and cells was detected using bioinformatics analysis and reverse transcription quantitative PCR. The impacts of PRDX1 on DLBCL cell proliferation, apoptosis, migration, invasion, and ferroptosis were assessed through a series of in vitro experiments. A xenograft tumor model was constructed to verify the roles of PRDX1 in vivo. Transcriptome sequencing was conducted to identify PRDX1-mediated signaling pathways. Anisomycin, an agonist of mitogen-activated protein kinase (MAPK), was used to explore the modulation of PRDX1 on the MAPK pathway.

RESULTS

PRDX1 expression was upregulated in DLBCL. PRDX1 knockdown inhibited DLBCL cell proliferation, migration, and invasion, promoted apoptosis, and suppressed xenograft tumor growth. PRDX1 knockdown boosted erastin-induced ferroptosis by increasing the levels of iron and MDA, while decreasing the levels of GSH. It also promoted COX2 protein expression and inhibited GPX4 and SLC7A11 protein levels. PRDX1 knockdown reduced the phosphorylation levels of MEK and ERK both under conditions with or without erastin induction. The MAPK/ERK pathway agonist anisomycin, significantly reversed the inhibitory effects of PRDX1 knockdown on the malignant behaviors of DLBCL cells and the promotion of ferroptosis.

CONCLUSION

PRDX1 knockdown facilitates erastin-induced ferroptosis and obstacles DLBCL progression by inhibiting the MAPK/ERK pathway, offering a potential treatment strategy for DLBCL treatment.