Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor with limited treatment options and poor patient survival. Circular RNAs (circRNAs) play crucial regulatory roles in the occurrence and development of various cancers, including PDAC. Here, using circRNA sequencing of diverse PDAC samples, we identified circRREB1 as an oncogenic circRNA that is significantly upregulated in PDAC and is correlated with an unfavorable patient prognosis. Functionally, loss of circRREB1 markedly inhibited glycolysis and stemness, while elevated circRREB1 elicited the opposite effects. Mechanistically, circRREB1 interacted with PGK1, disrupting the association between PTEN and PGK1 and increasing PGK1 phosphorylation to activate glycolytic flux. Moreover, circRREB1 promoted WNT7B transcription by directly interacting with YBX1 and facilitating its nuclear translocation, consequently activating the Wnt/β-catenin signaling pathway to maintain PDAC stemness. Overall, these results highlight circRREB1 as a key regulator of metabolic and stemness properties of PDAC.

中文翻译：

---

CircRREB1 介导代谢重编程和干性维持以促进胰腺导管腺癌进展


胰腺导管腺癌（PDAC）是一种高度致命的肿瘤，治疗选择有限，患者生存率较差。环状RNA（circRNA）在包括PDAC在内的多种癌症的发生和发展中发挥着至关重要的调节作用。在这里，通过对不同 PDAC 样本的 circRNA 测序，我们将 circRREB1 鉴定为一种致癌 circRNA，它在 PDAC 中显着上调，并且与不良的患者预后相关。从功能上讲，circRREB1 的缺失显着抑制糖酵解和干细胞性，而 circRREB1 的升高则引发相反的效果。从机制上讲，circRREB1 与 PGK1 相互作用，破坏 PTEN 和 PGK1 之间的关联，并增加 PGK1 磷酸化以激活糖酵解通量。此外，circRREB1通过直接与YBX1相互作用并促进其核转位来促进WNT7B转录，从而激活Wnt/β-catenin信号通路以维持PDAC干性。总的来说，这些结果凸显了 circRREB1 作为 PDAC 代谢和干性特性的关键调节因子。