Pkm, which codes for pyruvate kinase muscle isoforms, is a key gene in the glycolytic pathway. The PKM gene produces PKM1 and PKM2 through alternative splicing, with PKM2 being upregulated in most cancers and playing a crucial role in the Warburg effect, where cancer cells prefer aerobic glycolysis over oxidative phosphorylation for energy metabolism [1,2,3,5].

In hepatocellular carcinoma (HCC), antisense oligonucleotides (ASO) that switch PKM splicing from PKM2 to PKM1 inhibit tumor growth both in vitro and in vivo. In an orthotopic HCC xenograft mouse model, lead ASOs targeting PKM inhibited tumor growth. In a genetic HCC mouse model, a mouse-specific ASO induced Pkm splice switching and inhibited tumorigenesis without observable toxicity [1]. In a carotid artery injury model, Phb2 deficiency in vascular smooth muscle cells (VSMCs) facilitated PKM1/2 mRNA splicing to PKM2, enhanced glycolysis, and aggravated post-injury neointima formation. This shows that counteracting PKM2 splicing can maintain the contractile phenotype of VSMCs [4].

In conclusion, Pkm is essential in regulating glycolysis and its alternative splicing products, especially PKM2, are closely associated with cancer development. Mouse models, such as the genetic HCC mouse model and the carotid artery injury model, have been crucial in revealing the role of Pkm in cancer and vascular diseases, providing potential therapeutic targets for these conditions.