纤溶肝素通过驱动肝癌中 PFKFB4 的增强子介导转录重编程葡萄糖代谢

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2024-08-23 DOI:10.1016/j.canlet.2024.217190

Yizhe Liu , Qili Shi , Yanfang Liu , Xinrong Li , Zhen Wang , Shenglin Huang , Zhiao Chen , Xianghuo He

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引用次数: 0

摘要

DNA和RNA结合蛋白（DRBPs）是一种能与DNA和RNA分子结合的多功能蛋白。在这项研究中，我们发现纤丝蛋白（FBL）是一种关键的DRBP，它在肝癌组织与正常组织中上调，并与患者的预后相关。FBL 在体外和体内都能促进肝癌细胞的增殖。从机理上讲，FBL 与转录因子 KHSRP 相互作用，从而调节葡萄糖代谢相关基因的表达，导致葡萄糖代谢的重编程。具体来说，FBL 和 KHSRP 通过共同占据增强子和启动子元件，共同作用转录激活糖酵解酶 PFKFB4，从而进一步促进肝癌的生长。总之，这些发现提供了令人信服的证据，凸显了 FBL 作为肝癌细胞转录调控因子与 KHSRP 协同作用的作用。FBL/KHSRP-PFKFB4调控轴有望成为肝癌的预后指标和治疗靶点。意义：FBL在PFKFB4的转录激活中发挥了新的作用，导致肝癌中葡萄糖代谢的重编程。

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Fibrillarin reprograms glucose metabolism by driving the enhancer-mediated transcription of PFKFB4 in liver cancer

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.

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.