Deficiency of LIMA1 accelerates bladder cancer progression by disrupting PINK1/Parkin-mediated mitophagy

The LIM domain and actin-binding protein 1 (LIMA1), as a cytoskeletal-associated tumor suppressor, has not yet been clearly characterized in bladder cancer (BLCA). This study found that the cytoskeletal protein LIMA1 plays a key tumor-suppressing role in BLCA. Clinical analysis revealed that LIMA1 is significantly downregulated in tumor tissues and serum, with its low expression positively correlated with clinical stage, pathological grade, and recurrence risk, and predictive of poor prognosis. Functionally, LIMA1 knockout promotes tumor cell proliferation, migration, and invasion, and increases tumor volume by 1.8-fold in a mouse subcutaneous xenograft model. Mechanistically, database prediction and molecular docking confirmed that LIMA1 directly binds to PINK1, enhancing mitochondrial autophagy by activating the PINK1-Parkin pathway. The mitochondrial autophagy inducer uric acid A reverses the malignant phenotype caused by LIMA1 deficiency. In summary, this study reveals the inhibitory role of the LIMA1/PINK1/mitochondrial autophagy pathway in BLCA progression, providing a theoretical basis for novel therapeutic strategies targeting this pathway.