背景:膀胱癌(BC)是泌尿生殖系统最常见的恶性肿瘤之一。磷酸果糖激酶1(PFK-1)是PFK的成员之一,在重新编程癌症代谢中起着重要作用,如乳酸化改性。锌指E盒结合同源盒1(ZEB1)已被证明是许多癌症中的癌基因。因此,本研究旨在探讨PFK-1对BC发展过程中ZEB1的乳酸化作用。
方法:使用CCK-8试剂盒测量细胞活力。葡萄糖测定试剂盒和乳酸测定试剂盒用于检测葡萄糖利用和乳酸产生。纯化DNA并通过qRT-PCR定量。
结果:在本研究中,我们发现ZEB1在膀胱癌细胞中的表达水平显著升高.PFK-1表达受损抑制增殖,迁移,和BC细胞的侵袭,并在体内抑制肿瘤生长。我们随后发现PFK-1的敲减减少糖酵解,包括减少葡萄糖消耗,乳酸产量和总胞外酸化率(ECAR)。机械上,PFK-1抑制膀胱癌细胞的组蛋白乳酸化,从而抑制ZEB1的转录活性。
结论:我们的结果表明,PFK-1可以通过介导ZEB1的乳酸化抑制膀胱癌细胞的恶性表型。这些发现表明PFK-1是膀胱癌治疗的新的潜在靶标。
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.
CONCLUSIONS: 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.