Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Japan.
Translational Research Program, Osaka Medical College, Osaka, Japan.
Cancer Sci. 2021 Jan;112(1):41-50. doi: 10.1111/cas.14694. Epub 2020 Nov 4.
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.
对 microRNAs（miRNAs）调控系统的理解已成为生理/肿瘤学研究不可或缺的一部分。miRNAs 的组织和器官特异性是癌症研究中应考虑的关键特征。此外，癌症特异性能量代谢，即沃伯格效应，已被定位为癌症的一个关键特征。癌细胞中糖酵解途径的增强主要是沃伯格效应的特征。丙酮酸激酶 M1/2（PKM1/2）是复杂糖酵解系统的关键分子；它们的分布具有器官特异性。事实上，在各种癌细胞中都检测到 PKM2 的过表达。PKM 异构体通过异质核核糖核蛋白的选择性剪接产生。此外，多嘧啶 tract 结合蛋白 1（PTBP1）是癌细胞中 PKM2 产生所必需的。最近，几项专注于非编码 RNA 的研究阐明了 PTBP1 或 PKM2 的调控机制，包括 miRNA 的调控及其与癌症的关联。在这篇综述中，我们讨论了 miRNA 的器官特异性分布与 PTBP1 基因调控下 PKM 表达之间的紧密关系。此外，我们还重点关注了针对 PTBP1 的 miRNA 失调对沃伯格效应的影响。
