School of Pharmacy, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Basic Medical College, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Medicine (Baltimore). 2023 Oct 20;102(42):e35571. doi: 10.1097/MD.0000000000035571.
Hepatocellular carcinoma (HCC) is one of the most malignant tumors with the highest incidence and mortality in the world, causing a serious burden on society. Pyruvate kinase M2 (PKM2) is one of the principal metabolic enzymes involved in glycolysis. Studies have shown that PKM2 is highly expressed in HCC and can be translocated to the nucleus, where it interacts with various transcription factors and proteins such as hypoxia-inducible factor-1α, sterol regulatory element-binding protein 1a, signal transducer and activator of transcription 3, nuclear factor erythroid 2-like 2 and histone H3, exerting non-metabolic enzyme functions to regulate the cell cycle, proliferation, apoptosis, immune escape, migration, and invasion, as well as HCC angiogenesis and tumor microenvironment. This review is focused on the recent progress of PKM2 interacting with various transcription factors and proteins affecting the onset and development of HCC, as well as natural drugs and noncoding RNA impacting diverse biological functions of liver cancer cells by regulating PKM2 non-metabolic enzyme functions, thereby providing valuable directions for the prognosis improvement and molecular targeted therapy of HCC in the future.
肝细胞癌（HCC）是世界上发病率和死亡率最高的最恶性肿瘤之一，给社会造成了严重负担。丙酮酸激酶 M2（PKM2）是参与糖酵解的主要代谢酶之一。研究表明，PKM2 在 HCC 中高表达，并可易位到细胞核内，与各种转录因子和蛋白质相互作用，如缺氧诱导因子-1α、固醇调节元件结合蛋白 1a、信号转导和转录激活因子 3、核因子红系 2 样 2 和组蛋白 H3，发挥非代谢酶功能，调节细胞周期、增殖、凋亡、免疫逃逸、迁移和侵袭，以及 HCC 血管生成和肿瘤微环境。本综述重点介绍了 PKM2 与各种转录因子和蛋白质相互作用，影响 HCC 的发生和发展的最新进展，以及天然药物和非编码 RNA 通过调节 PKM2 的非代谢酶功能影响肝癌细胞的多种生物学功能，为未来 HCC 的预后改善和分子靶向治疗提供了有价值的方向。
