FABP5 Confers Resistance to Drug-Induced ROS Toxicity in Cervical Cancer Cell lines by Suppressing the PPARγ/CPT1A Signaling Pathway

Background Fatty acid-binding protein 5 (FABP5) is highly expressed in various tumor cell types and associated with cancer progression. It is also associated with resistance to multiple drugs. Nevertheless, there is currently no reports regarding the role of FABP5 in cervical cancer in conferring resistance to chemotherapy-induced reactive oxygen species (ROS). Method In this study, online bioinformatics platforms and immunohistochemistry analyzed the FABP5 expression in cervical cancer. Subsequently, stable cell lines with FABP5 knockdown and overexpression were established in vitro. RNA-seq was performed to analyze gene expression differences induced by FABP5. Cell experiments were conducted using cisplatin and paclitaxel as drug-induced ROS models, jointly validating FABP5's role in conferring resistance to drug-induced ROS in cervical cancer cell lines. Result FABP5, as an oncogene, exhibits significantly elevated expression in cervical cell lines. Notably, FABP5 confers resistance to both cisplatin and paclitaxel. RNA-seq results indicate that FABP5 functions in fatty acid metabolism pathways.Overexpression of FABP5 shifts cellular metabolism toward enhanced fatty acid storage capacity. This is achieved by suppressing the PPARγ/CPT1A pathway and respiratory chain component ATP5A1. Drug-induced ROS activates the PPARγ/CPT1A pathway, thereby upregulating respiratory chain component ATP5A1 and reducing intracellular lipid levels. Conclusion FABP5 increases cells’ reserves while maintaining cells in a low ROS state by inhibiting the PPARγ/CPT1A signaling pathway and downregulating the expression of respiratory chain component ATP5A1. The PPARγ/CPT1A signaling pathway may represent one of the key mechanisms by which cells defend against exogenous ROS.