A comprehensive analysis of the pyruvate kinase M1/2 (PKM) in human cancer.

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY

Gene Pub Date : 2025-02-10 Epub Date: 2024-12-07 DOI:10.1016/j.gene.2024.149155

Shuaishuai Xue, Ziyi Luo, Yangqi Mao, Siyuan Liu

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引用次数: 0

Abstract

Background: Pyruvate Kinase Muscle Isozyme (PKM), as a member of the pyruvate kinase, is a key enzyme in glycolysis. Numerous tumors have demonstrated its oncogenic properties. There is, however, no pan-carcinogenic analysis for PKM.

Methods: A thorough analysis of PKM across various types of cancer was carried out using bioinformatics resources like The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) database. This study involved analyzing the role of PKM in 33 various types of cancers, along with investigating gene expressions, survival rates, clinical importance, genetic changes, immune system presence, and related signaling pathways. Furthermore, we evaluated the effects of PKM knockdown on human colon carcinoma, and glioblastoma cell lines by in vitro experimentation.

Results: In most tumors, PKM expression was markedly increased and was associated with unfavorable overall survival (OS) in certain individuals. In addition, infiltration of macrophages was associated with PKM expression in various tumors. PKM was linked to glycolysis/gluconeogenesis, HIF-1 signaling, carbon metabolism, and NADPH regeneration in a mechanistic manner. Additionally, cell experiments showed that the knockdown of PKM could reduce the proliferation and migration abilities while promoting the apoptosis of Caco-2, and U-87 MG cells.

Conclusion: PKM controls immune cell infiltration, impacts patient outcomes in various types of cancer, and plays an essential role in proliferation and migration in some tumor cells by affecting glycometabolism. The PKM molecule may serve as a potential prognostic biomarker and therapeutic target for human cancers.

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丙酮酸激酶M1/2 （PKM）在人类癌症中的综合分析。

背景：丙酮酸激酶肌同工酶（PKM）作为丙酮酸激酶的一员，是糖酵解的关键酶。许多肿瘤已证实其致癌特性。然而，没有对PKM的泛致癌分析。方法：利用美国国家癌症研究所临床蛋白质组学肿瘤分析联盟（CPTAC）和癌症基因组图谱（TCGA）数据库等生物信息学资源，对不同类型癌症的PKM进行深入分析。这项研究包括分析PKM在33种不同类型癌症中的作用，以及研究基因表达、生存率、临床重要性、遗传变化、免疫系统存在和相关信号通路。此外，我们还通过体外实验评估了PKM敲除对人结肠癌和胶质母细胞瘤细胞系的影响。结果：在大多数肿瘤中，PKM表达显著升高，并与某些个体的不利总生存期（OS）相关。此外，巨噬细胞的浸润与各种肿瘤中PKM的表达有关。PKM与糖酵解/糖异生、HIF-1信号、碳代谢和NADPH再生有关。此外，细胞实验表明，PKM的下调可降低Caco-2和U-87 MG细胞的增殖和迁移能力，促进其凋亡。结论：PKM控制免疫细胞浸润，影响各种类型肿瘤患者的预后，并通过影响糖代谢在某些肿瘤细胞的增殖和迁移中发挥重要作用。PKM分子可作为人类癌症的潜在预后生物标志物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.