Pkm, which codes for pyruvate kinase muscle isoforms, is a key gene in the glycolytic pathway. PKM1 and PKM2 are alternative-splice isoforms of the PKM gene. PKM2, in particular, is upregulated in most cancers and is involved in the Warburg effect, where cancer cells prefer aerobic glycolysis over oxidative phosphorylation for energy metabolism [1,2,3,5].

In an orthotopic HCC xenograft mouse model, antisense oligonucleotides (ASO) that switch PKM splicing from PKM2 to PKM1 inhibited tumor growth. In a genetic HCC mouse model, a surrogate mouse-specific ASO induced Pkm splice switching and inhibited tumorigenesis without observable toxicity [1]. Also, in a carotid artery injury model (an in vivo model related to vascular diseases), PHB2 deficiency facilitated PKM1/2 mRNA splicing and reversion from PKM1 to PKM2, enhancing glycolysis in vascular smooth muscle cells (VSMCs) and aggravating post-injury neointima formation, suggesting a role of Pkm splicing in VSMC-related vascular diseases [4].

In conclusion, Pkm plays a crucial role in energy metabolism, especially in the context of cancer and certain vascular diseases. Gene-targeting mouse models, such as those used in HCC and vascular injury studies, have been instrumental in revealing the role of Pkm splicing in tumorigenesis and VSMC phenotypic transition, providing potential therapeutic targets for these diseases.