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

• Published in: Cancer science Vol. 112; no. 1; pp. 41 - 50
• Main Authors: Taniguchi, Kohei, Uchiyama, Kazuhisa, Akao, Yukihiro
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.01.2021; John Wiley and Sons Inc
• Subjects: Alternative splicing; Alternative Splicing - genetics; Binding sites; Brain cancer; Cancer; Carrier Proteins - genetics; Colorectal cancer; Energy metabolism; Energy Metabolism - genetics; Gene expression; Gene regulation; Gene Regulatory Networks - genetics; Glycolysis; Humans; Isoforms; Kinases; Liver cancer; Membrane Proteins - genetics; Metabolism; microRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Non-coding RNA; organ‐specificity; Physiology; PKM; Polypyrimidine Tract-Binding Protein - genetics; PTBP1; Pyruvate kinase; Pyruvate Kinase - genetics; Pyruvic acid; Review; Ribonucleoproteins; Thyroid Hormone-Binding Proteins; Thyroid Hormones - genetics; Transcription factors; Tumors; Warburg effect; organ-specificity; PTBP1; microRNA; PKM; Warburg effect
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.14694

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. In this review, we discuss the miRNA‐mediated regulation of PTBP1 and PKM isoforms. In particular, we elaborate on the following points. First, under physiological conditions, the expression of PTBP1 and PKM isoforms is regulated by miRNAs that are unevenly distributed throughout the organs. Second, during carcinogenesis, dysregulation of PTBP1‐targeting miRNAs affects cancer‐specific energy metabolism in various types of cancer cells through PKM2 upregulation.