A candidate prognostic biomarker: TFEB inhibits tumor progression via elevating CDKN1A in bladder cancer

Abstract

Bladder cancer(BC) is among the most prevalent malignancies in the world, with 549,393 new cases documented in 2018, and most BC patients have a poor prognosis. Transcription factor EB (TFEB) is considered a crucial controller of lysosomal-associated diseases, but a growing number of research in recent years have reported that TFEB plays other functions in tumors independent of lysosomal autophagy. In this study, we aimed to assess whether TFEB is a biomarker for BC and a molecular target for BC therapy. TFEB was lowly expressed in BC tissues relative to paracancerous tissues, and its elevated expression was strongly associated to a better prognosis for BC patients. TFEB overexpression markedly suppressed cell proliferation, limited cell migration, and accelerated apoptosis. Tumor growth in vivo was also suppressed. Mechanistically, we found that TFEB promoted CDKN1A expression by binding to the upstream progenitor of the CDKN1A promoter, which was also dependent on p53. Finally, Immune cell infiltration in BC tissues, PDL-1 expression, and Single-cell RNA sequencing data revealed immunotherapy may have a positive correlation with TFEB expression. Our study identifies that TFEB regulates CDKN1A in BC and has a positive prognostic value, while its expression is also positively correlated with immune cell infiltration. Therefore, TFEB may represent a recent therapeutic target for BC.