FAM72A Knockdown Drives Cell Mitophagy and Pyroptosis in Ovarian Cancer Via the PINK1/Parkin Pathway

This study explored the role of Family with Sequence Similarity 72 Member A (FAM72A) in regulating Mitophagy and Pyroptosis via the PINK1/Parkin pathway in ovarian Cancer (OC). Bioinformatics analysis and clinical tissue and cell assays revealed that FAM72A was significantly overexpressed in OC. Silencing FAM72A in OC cells suppressed proliferation, invasion, and migration, while promoting Apoptosis. Additionally, FAM72A knockdown increased mitochondrial ROS levels, autophagosome-mitochondria colocalization, and the LC3II/I ratio and reduced p62 expression, mitochondrial membrane potential, and ATP levels in OC cells. Downregulation of FAM72A upregulated PINK1 and Parkin expression and increased the expression of pyroptosis-related markers including NLRP3, ASC, cleaved Caspase-1, IL-1β, and IL-18 in OC cells. Furthermore, the inhibitory effect of FAM72A knockdown was reversed by treating cells with mitochondrial inhibitors or by specifically knocking down PINK1. In vivo experiments confirmed that FAM72A promoted tumor growth by inhibiting the PINK1/Parkin pathway. Conclusively, FAM72A knockdown drives Mitophagy and Pyroptosis in OC by activating the PINK1/Parkin pathway, highlighting its potential as a therapeutic target for OC.