Puckett Dexter L, Alquraishi Mohammed, Chowanadisai Winyoo, Bettaieb Ahmed
Department of Nutrition, University of Tennessee Knoxville, Knoxville, TN 37996, USA.
Department of Nutrition, Oklahoma State University, Stillwater, OK 74078, USA.
Int J Mol Sci. 2021 Jan 25;22(3):1171. doi: 10.3390/ijms22031171.
Pyruvate kinase is a key regulator in glycolysis through the conversion of phosphoenolpyruvate (PEP) into pyruvate. Pyruvate kinase exists in various isoforms that can exhibit diverse biological functions and outcomes. The pyruvate kinase isoenzyme type M2 (PKM2) controls cell progression and survival through the regulation of key signaling pathways. In cancer cells, the dimer form of PKM2 predominates and plays an integral role in cancer metabolism. This predominance of the inactive dimeric form promotes the accumulation of phosphometabolites, allowing cancer cells to engage in high levels of synthetic processing to enhance their proliferative capacity. PKM2 has been recognized for its role in regulating gene expression and transcription factors critical for health and disease. This role enables PKM2 to exert profound regulatory effects that promote cancer cell metabolism, proliferation, and migration. In addition to its role in cancer, PKM2 regulates aspects essential to cellular homeostasis in non-cancer tissues and, in some cases, promotes tissue-specific pathways in health and diseases. In pursuit of understanding the diverse tissue-specific roles of PKM2, investigations targeting tissues such as the kidney, liver, adipose, and pancreas have been conducted. Findings from these studies enhance our understanding of PKM2 functions in various diseases beyond cancer. Therefore, there is substantial interest in PKM2 modulation as a potential therapeutic target for the treatment of multiple conditions. Indeed, a vast plethora of research has focused on identifying therapeutic strategies for targeting PKM2. Recently, targeting PKM2 through its regulatory microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) has gathered increasing interest. Thus, the goal of this review is to highlight recent advancements in PKM2 research, with a focus on PKM2 regulatory microRNAs and lncRNAs and their subsequent physiological significance.
丙酮酸激酶是糖酵解过程中的关键调节因子，可将磷酸烯醇式丙酮酸（PEP）转化为丙酮酸。丙酮酸激酶存在多种同工型，可表现出不同的生物学功能和结果。丙酮酸激酶M2型同工酶（PKM2）通过调节关键信号通路来控制细胞进程和存活。在癌细胞中，PKM2的二聚体形式占主导地位，并在癌症代谢中发挥不可或缺的作用。这种无活性二聚体形式的优势促进了磷酸代谢物的积累，使癌细胞能够进行高水平的合成加工以增强其增殖能力。PKM2因其在调节对健康和疾病至关重要的基因表达和转录因子方面的作用而受到认可。这一作用使PKM2能够发挥深远的调节作用，促进癌细胞的代谢、增殖和迁移。除了在癌症中的作用外，PKM2还调节非癌组织中细胞稳态所必需的方面，在某些情况下，还促进健康和疾病中的组织特异性途径。为了深入了解PKM2在不同组织中的特异性作用，已经针对肾脏、肝脏、脂肪和胰腺等组织展开了研究。这些研究的结果加深了我们对PKM2在癌症以外的各种疾病中功能的理解。因此，将PKM2作为多种疾病潜在治疗靶点进行调控引起了广泛关注。事实上，大量研究都集中在寻找靶向PKM2的治疗策略。最近，通过其调控性微小RNA、长链非编码RNA（lncRNA）和环状RNA（circRNA）靶向PKM2越来越受到关注。因此，本综述的目的是突出PKM2研究的最新进展，重点关注PKM2调控性微小RNA和lncRNA及其随后的生理意义。
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