DNA 和 RNA 结合蛋白 (DRBP) 是能够结合 DNA 和 RNA 分子的多功能蛋白质。在这项研究中，我们确定原纤维蛋白 (FBL) 是一种关键的 DRBP，与正常组织相比，它在肝癌组织中表达上调，并且与患者预后相关。 FBL在体外和体内均促进肝癌细胞的增殖。从机制上讲，FBL与转录因子KHSRP相互作用，从而调节与葡萄糖代谢相关的基因的表达并导致葡萄糖代谢的重编程。具体来说，FBL和KHSRP共同作用，通过共占据增强子和启动子元件，转录激活糖酵解酶PFKFB4，从而进一步促进肝癌生长。总的来说，这些发现提供了令人信服的证据，强调了 FBL 与 KHSRP 结合作为肝癌细胞中转录调节因子的作用。 FBL/KHSRP-PFKFB4 调节轴具有作为肝癌预后指标和治疗靶点的潜力。意义：FBL 在 PFKFB4 转录激活中的新作用，导致肝癌中葡萄糖代谢重编程。版权所有 © 2024。由 Elsevier B.V. 出版。

DNA- and RNA-binding proteins (DRBPs) are versatile proteins capable of binding to both DNA and RNA molecules. In this study, we identified fibrillarin (FBL) as a key DRBP that is upregulated in liver cancer tissues vs. normal tissues and is correlated with patient prognosis. FBL promotes the proliferation of liver cancer cells both in vitro and in vivo. Mechanistically, FBL interacts with the transcription factor KHSRP, thereby regulating the expression of genes involved in glucose metabolism and leading to the reprogramming of glucose metabolism. Specifically, FBL and KHSRP work together to transcriptionally activate the glycolytic enzyme PFKFB4 by co-occupying enhancer and promoter elements, thereby further promoting liver cancer growth. Collectively, these findings provide compelling evidence highlighting the role of FBL as a transcriptional regulator in liver cancer cells, working in conjunction with KHSRP. The FBL/KHSRP-PFKFB4 regulatory axis holds potential as both a prognostic indicator and a therapeutic target for liver cancer. SIGNIFICANCE: A novel role of FBL in the transcriptional activation of PFKFB4, leading to glucose metabolism reprogramming in liver cancer.Copyright © 2024. Published by Elsevier B.V.