Pkm, encoding pyruvate kinase muscle isoforms, is crucial in the glycolytic pathway. Pyruvate kinase catalyzes the final and rate-limiting step of glycolysis, converting Phosphoenolpyruvate (PEP) to Pyruvate. PKM1 and PKM2 are formed by alternative splicing of the PKM gene transcript. PKM2, upregulated in most cancers, is involved in the Warburg effect, where cancer cells prefer aerobic glycolysis over oxidative phosphorylation for energy metabolism [1,3,4].

In a genetic HCC mouse model, a surrogate mouse-specific ASO induced Pkm splice-switching from the cancer-associated PKM2 to the PKM1 isoform, inhibiting tumorigenesis without observable toxicity. This shows that altering Pkm splicing can be a potential therapeutic strategy for HCC [1]. In colorectal cancer, the lncRNA LINC01852 inhibits SRSF5-mediated alternative splicing of Pkm, decreasing the production of PKM2 and attenuating chemoresistance [2].

In conclusion, Pkm, through its alternative splicing products PKM1 and PKM2, plays a vital role in energy metabolism, especially in the context of cancer. The use of genetic mouse models, like the HCC mouse model, has revealed the potential of targeting Pkm splicing as a therapeutic approach for cancer, highlighting the importance of Pkm in cancer-related metabolic reprogramming.