<br>PTBP1靶向microRNA通过调节PKM1/M2剪接调节癌症特异性能量代谢,Cancer Science

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PTBP1靶向microRNA通过调节PKM1/M2剪接调节癌症特异性能量代谢
Cancer Science ( IF 4.5 ) Pub Date : 2020-10-18 , DOI: 10.1111/cas.14694
Kohei Taniguchi _{1,

2} , Kazuhisa Uchiyama ₁ , Yukihiro Akao ₃

Affiliation

了解 microRNA (miRNA) 调控系统已成为生理/肿瘤学研究不可或缺的一部分。组织和器官特异性是癌症研究中应考虑的 miRNA 的关键特征。此外，癌症特异性能量代谢（称为瓦尔堡效应）已被定位为关键的癌症特征。癌细胞中糖酵解途径的增强是瓦尔堡效应的主要特征。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，已在多种癌细胞中检测到 PKM2 过度表达。 PKM 亚型是通过异质核核糖核蛋白的选择性剪接产生的。此外，多聚嘧啶束结合蛋白 1 (PTBP1) 对于癌细胞中 PKM2 的产生至关重要。最近，几项关注非编码 RNA 的研究阐明了 PTBP1 或 PKM2 调节机制，包括 miRNA 的控制及其与癌症的关联。在这篇综述中，我们讨论了PTBP1基因调控背景下 miRNA 的器官特异性分布与 PKM 表达之间的密切关系。此外，我们重点关注PTBP1靶向 miRNA 失调对 Warburg 效应的影响。

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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.

更新日期：2020-10-18

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