To investigate the role of histone lactylation, specifically H3K18la, in the metabolic reprogramming of aggressive bladder cancer (BC) and its correlation with glycolysis.
Approach:
Data Analysis: Analyzed single-cell RNA sequencing dataset GSE135337 to assess glycolysis and histone lactylation levels in BC samples.
Experimental Techniques: Utilized western blotting and immunofluorescence to detect histone lactylation levels; employed glycolysis inhibitors and LDHA knockdown to study effects on BC growth.
Gene Screening: Conducted CUT&Tag and RNA-seq analyses to identify potential target genes of H3K18la.
Key Findings:
Increased glycolytic activity and histone lactylation (H3K18la) were associated with poor prognosis in BC patients.
Inhibition of glycolysis or LDHA knockdown resulted in suppressed BC growth in both in vitro and in vivo models.
Four potential target genes (AHNAK2, PVR, SLC7A11, SREBF1) were identified as being associated with BC growth and invasion.
Interpretation:
Glycolysis is linked to H3K18la enrichment at specific gene loci, establishing a correlative epigenetic network in aggressive BC progression.
Limitations:
The study is based on a single dataset, which may limit the generalizability of the findings.
Further validation in larger cohorts and additional experimental models is needed.
Conclusion:
The findings reveal connections between lactate metabolism reprogramming and epigenetic regulation, highlighting potential therapeutic strategies targeting lactylation in BC.
