Single-cell analysis reveals the molecular regulatory mechanisms of high mobility group box 1 in prostate cancer development and progression.

High mobility group box 1 (HMGB1), which plays a crucial role in cancer progression, remains incompletely elucidated due to the high heterogeneity and complex tumor microenvironment of prostate cancer (PCa). This study, through single-cell transcriptomic analysis, provided a comprehensive elucidation of cellular heterogeneity in PCa tissues and revealed the essential role of HMGB1 in the progression of PCa by using in vitro cell experiments. Single-cell analysis revealed that an epithelial subpopulation with high levels of HMGB1 (HMGB1+ Malignant LE) significantly increased in PCa tissues, which was closely correlated with the malignant characteristics of the tumor. KEGG enrichment analysis revealed that pathways associated with autophagy, mitophagy, and apoptosis were significantly enriched in the HMGB1+ Malignant LE sub-group. In vitro cell experiments further confirmed that knocking down HMGB1 significantly inhibited the proliferation, migration, and invasive capacity of PCa cells, while inducing cellular apoptosis and cell cycle arrest. These findings suggest that HMGB1 promotes PCa malignancy by modulating tumor cell metabolism and cellular cycle progression. This study provides novel insights into the role of HMGB1 in PCa and lays theoretical groundwork for the development of therapeutic strategies targeting HMGB1.