Li Xiangyu, Kim Woonghee, Arif Muhammad, Gao Chunxia, Hober Andreas, Kotol David, Strandberg Linnéa, Forsström Björn, Sivertsson Åsa, Oksvold Per, Turkez Hasan, Grøtli Morten, Sato Yusuke, Kume Haruki, Ogawa Seishi, Boren Jan, Nielsen Jens, Uhlen Mathias, Zhang Cheng, Mardinoglu Adil
Science for Life Laboratory, KTH-Royal Institute of Technology, SE-17165 Stockholm, Sweden.
Department of Chemistry and Molecular Biology, University of Gothenburg, SE-41296 Gothenburg, Sweden.
Cancers (Basel). 2021 Jan 19;13(2):348. doi: 10.3390/cancers13020348.
Pyruvate kinase muscle type () is a key enzyme in glycolysis and plays an important oncological role in cancer. However, the association of expression and the survival outcome of patients with different cancers is controversial. We employed systems biology methods to reveal prognostic value and potential biological functions of transcripts in different human cancers. Protein products of transcripts were shown and detected by western blot and mass spectrometry analysis. We focused on different transcripts of and investigated the associations between their mRNA expression and the clinical survival of the patients in 25 different cancers. We find that the transcripts encoding PKM2 and three previously unstudied transcripts, namely ENST00000389093, ENST00000568883, and ENST00000561609, exhibited opposite prognostic indications in different cancers. Moreover, we validated the prognostic effect of these transcripts in an independent kidney cancer cohort. Finally, we revealed that ENST00000389093 and ENST00000568883 possess pyruvate kinase enzymatic activity and may have functional roles in metabolism, cell invasion, and hypoxia response in cancer cells. Our study provided a potential explanation to the controversial prognostic indication of , and could invoke future studies focusing on revealing the biological and oncological roles of these alternative spliced variants of .
丙酮酸激酶肌肉型（）是糖酵解中的关键酶，在癌症中发挥着重要的肿瘤学作用。然而，其表达与不同癌症患者生存结局之间的关联存在争议。我们采用系统生物学方法来揭示其转录本在不同人类癌症中的预后价值和潜在生物学功能。通过蛋白质印迹法和质谱分析展示并检测了转录本的蛋白质产物。我们聚焦于的不同转录本，并研究了它们的mRNA表达与25种不同癌症患者临床生存之间的关联。我们发现，编码PKM2的转录本以及三个先前未研究的转录本，即ENST00000389093、ENST00000568883和ENST00000561609，在不同癌症中表现出相反的预后指征。此外，我们在一个独立的肾癌队列中验证了这些转录本的预后作用。最后，我们揭示了ENST00000389093和ENST00000568883具有丙酮酸激酶酶活性，并且可能在癌细胞的代谢、细胞侵袭和缺氧反应中发挥功能作用。我们的研究为关于的有争议的预后指征提供了一个潜在解释，并可能引发未来专注于揭示这些选择性剪接变体的生物学和肿瘤学作用的研究。
