LRP8 Regulates Lipid Metabolism to Stimulate Malignant Progression and Cisplatin Resistance in Bladder Cancer.

Abstract

Low-density lipoprotein receptor-related protein 8 (LRP8) is a crucial regulator of lipid metabolism and is implicated in the development and treatment of various cancers. However, its role in bladder cancer (BCa) remains unknown. We analyzed LRP8 expression in BCa using the TCGA database and clinical samples. We manipulated LRP8 expression in tumor cell lines using siRNA or overexpression plasmid transfection. Cell proliferation, migration, invasion, apoptosis, and drug resistance were assessed through CCK-8, transwell, flow cytometry, and IC₅₀ assays. Additionally, a rescue experiment confirmed the association between LRP8 and lipid metabolism. LRP8 was significantly upregulated in BCa tissues and cells. Knockdown of LRP8 reduced tumor cell proliferation, migration, invasion, and increased apoptosis while enhancing cisplatin sensitivity. Overexpression of LRP8 boosted malignant progression and cisplatin resistance in tumor cells. The expression level of LRP8 is positively linked with the expression of lipid metabolism-related genes, phospholipid accumulation, and triglyceride accumulation. Notably, inhibiting lipid metabolism reversed the malignant progression and cisplatin resistance induced by LRP8 overexpression. LRP8 could promote BCa malignant progression and cisplatin resistance through lipid metabolism regulation.