The mechanism of PFK-1 in the occurrence and development of bladder cancer by regulating ZEB1 lactylation

Background Bladder cancer (BC) is one of the most common malignancies of the genitourinary system.

Phosphofructokinase 1 (PFK-1) is one of member of PFK, which plays an important role in reprogramming cancer metabolism, such as lactylation modification.

Zinc finger E-box-binding homeobox 1 (ZEB1) has been demonstrated to be a oncogene in many cancers.

Therefore, this study was performed to explore the effects of PFK-1 on the lactylation of ZEB1 in BC development.

Methods Cell viability was measured using the CCK-8 kit.

The glucose assay kit and lactate assay kit were used to detect glucose utilization and lactate production.

The DNA was purified and quantified by qRT-PCR.

Results In the present study, we found that ZEB1 expression levels were significantly elevated in bladder cancer cells.

Impaired PFK-1 expression inhibits proliferation, migration, and invasion of BC cells and suppresses tumour growth in vivo.

We subsequently found that knockdown of PFK-1 decreases glycolysis, including reduced glucose consumption, lactate production and total extracellular acidification rate (ECAR).

Mechanistically, PFK-1 inhibits histone lactylation of bladder cancer cells, and thus inhibits the transcription activity of ZEB1.

Conclusion Our results suggest that PFK-1 can inhibit the malignant phenotype of bladder cancer cells by mediating the lactylation of ZEB1.

These findings suggested PFK-1 to be a new potential target for bladder cancer therapy.