PTBP1-targeting microRNAs regulate cancer-specific energy metabolism through the modulation of PKM1/M2 splicing.

Understanding of the microRNAs (miRNAs) regulatory system has become indispensable for physiological/oncological research. Tissue and organ specificities are key features of miRNAs that should be accounted for in cancer research. Further, cancer-specific energy metabolism, referred to as the Warburg effect, has been positioned as a key cancer feature. Enhancement of the glycolysis pathway in cancer cells is what primarily characterizes the Warburg effect. Pyruvate kinase M1/2 (PKM1/2) are key molecules of the complex glycolytic system; their distribution is organ-specific. In fact, PKM2 overexpression has been detected in various cancer cells. PKM isoforms are generated by alternative splicing by heterogeneous nuclear ribonucleoproteins. In addition, polypyrimidine tract-binding protein 1 (PTBP1) is essential for the production of PKM2 in cancer cells. Recently, several studies focusing on non-coding RNA elucidated PTBP1 or PKM2 regulatory mechanisms, including control by miRNAs, and their association with cancer. In this review, we discuss the strong relationship between the organ-specific distribution of miRNAs and the expression of PKM in the context of PTBP1 gene regulation. Moreover, we focus on the impact of PTBP1-targeting miRNA dysregulation on the Warburg effect.