PYCR2 Knockdown Suppresses the Proliferation, Migration, and Invasion of Esophageal Squamous Cell Carcinoma by the KEAP1-Nrf2 Pathway to Induce Ferroptosis

Abstract

Background: Pyrroline-5-Carboxylate Reductase 2 (PYCR2) demonstrates abnormal expression in various tumors and is intricately associated with tumor progression and prognosis. However, its expression and roles in esophageal squamous cell carcinoma (ESCC) remain unknown. The objective of this research is to explore the expression, effects, and underlying mechanisms of PYCR2 in ESCC. Methods: In this study, we performed immunohistochemical analysis on ESCC tissues to assess PYCR2 expression levels and their correlation with clinical parameters. Subsequently, we utilized in vitro assays and RNA sequencing to elucidate the functional roles of PYCR2 in ESCC cells. The primary objective was to comprehend the impact of PYCR2 on key cellular processes, including proliferation, migration, invasion, apoptosis, and its potential involvement in ferroptosis through the kelch-like ECH-associated protein 1 (KEAP1)-Nuclear factor erythroid-2 (NRF2) pathway. Results: Our findings suggest an upregulation of PYCR2 expression in ESCC, which correlates with a poorer prognosis in patients exhibiting increased PYCR2 levels (p < 0.05). Knocking down PYCR2 inhibits proliferation, migration, invasion, and epithelial-mesenchymal transformation (EMT), while concurrently promoting apoptosis (p < 0.05). Furthermore, our results indicate that PYCR2 knockdown induces ferroptosis by inhibiting the KEAP1-Nrf2 pathway. Conclusion: In conclusion, this study suggests that PYCR2 plays a crucial role in the malignant progression of ESCC and emerges as a promising new biomarker and potential therapeutic target in ESCC.