YTHDF2-induced LDHA inhibition promotes preeclampsia via the Hedgehog signaling pathway

Background: Lactate dehydrogenase (LDHA) is a key enzyme catalyzing the conversion of pyruvate to lactic acid in anaerobic glycolysis, but its role in preeclampsia (PE) remains unclear. Methods: Western blotting and immunohistochemistry (IHC) were performed to detect LDHA expression in PE tissues. Cell proliferation, migration, and invasion were detected by CCK-8 assay, EdU assay, and transwell assay after LDHA dysregulation. YTHDF2 expression in PE tissues was explored by IHC. The regulatory effect of YTHDF2 on LDHA was confirmed by correlation analysis and Western blotting. The mechanism underlying the involvement of LDHA in PE progression was demonstrated via gene set enrichment analysis and Western blotting. Results: LDHA was downregulated in PE tissues compared to normal placental tissues. Knockdown of LDHA significantly inhibited the proliferation, migration and invasion of trophocytes. YTHDF2 was overexpressed in PE tissues, and YTHDF2 silencing promoted LDHA expression. LDHA inhibition in trophocytes suppressed the Hedgehog signaling pathway. Conclusion: This study confirmed that YTHDF2-induced LDHA downregulation suppresses the proliferation, migration and invasion of trophocytes, leading to PE progression. LDHA has the potential to act as a novel therapeutic target for PE patients.