Discovery of Functional Alternatively Spliced PKM Transcripts in Human Cancers.
Simple Summary: Pyruvate kinase muscle type (PKM) is a key enzyme in glycolysis and is a mediator of the Warburg effect in tumors. The association of PKM with survival of cancer patients is controversial. In this study, we investigated the associations of the alternatively spliced transcripts of PKM...
| Published in: | Cancers Vol. 13; no. 2; pp. 348 - 349 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
| Format: | pictorial research tables/charts Journal Article |
| Published: |
MDPI
Jan2021
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=148343741&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 148343741 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Jan2021 vid: 13 iid: 2 pid: 97109 pub: MDPI artinfo: ui: 148343741 148343741 148343741 10.3390/cancers13020348 148343741 ppf: 348 ppct: 1 formats: tig: atl: Discovery of Functional Alternatively Spliced PKM Transcripts in Human Cancers. aug: au: 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 affil: Science for Life Laboratory, KTH—Royal Institute of Technology, SE-17165 Stockholm, Sweden sug: subj: Transferases Analysis Neoplasms Prognosis Human Cancer Patients Blotting, Western Mass Spectrometry MicroRNA Analysis RNA Analysis Gene Expression Profiling Transferases Metabolism In Vitro Studies ab: Simple Summary: Pyruvate kinase muscle type (PKM) is a key enzyme in glycolysis and is a mediator of the Warburg effect in tumors. The association of PKM with survival of cancer patients is controversial. In this study, we investigated the associations of the alternatively spliced transcripts of PKM with cancer patients' survival outcomes and explained the conflicts in previous studies. We discovered three poorly studied alternatively spliced PKM transcripts that exhibited opposite prognostic indications in different human cancers based on integrative systems analysis. We also detected their protein products and explored their potential biological functions based on in-vitro experiments. Our analysis demonstrated that alternatively spliced transcripts of not only PKM but also other genes should be considered in cancer studies, since it may enable the discovery and targeting of the right protein product for development of the efficient treatment strategies. Pyruvate kinase muscle type (PKM) is a key enzyme in glycolysis and plays an important oncological role in cancer. However, the association of PKM 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 PKM 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 PKM 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 PKM, and could invoke future studies focusing on revealing the biological and oncological roles of these alternative spliced variants of PKM. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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