Abstract

Microtubule-associated protein 1 light chain 3 beta (MAP1LC3B, LC3B) is a core autophagy-related protein, yet its functional role in bladder cancer remains incompletely understood. In this study, we aimed to clarify the expression pattern, biological function, and molecular mechanism of LC3B in bladder cancer and to further assess its broader clinical relevance across human cancers. Single-cell RNA sequencing revealed that LC3B is predominantly expressed in bladder cancer epithelial cells and is closely associated with cell cycle-related pathways. Functional studies in T24T and J82 bladder cancer cells revealed that LC3B knockout markedly suppressed tumor cell proliferation both in vitro and in vivo . Mechanistically, LC3B promoted G1/S phase transition by enhancing Sp1-mediated Cyclin D1 transcription while repressing p27 expression, thereby driving bladder cancer cell proliferation. Additional pan-cancer analyses showed that LC3B is aberrantly expressed across multiple tumor types and is significantly associated with tumor stage, genomic instability, and patient prognosis. Gene set enrichment analyses further suggested that LC3B may participate in transcriptional and metabolic reprogramming, supporting a noncanonical function that appears to be independent of LC3B lipidation. Collectively, these findings identify LC3B as a critical regulator of bladder cancer cell proliferation through the Sp1–Cyclin D1/p27 axis and provide new insight into its potential clinical relevance in bladder cancer and other malignancies.