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Discovery of Functi...
Discovery of Functional Alternatively Spliced PKM Transcripts in Human Cancers
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- Li, Xiangyu (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Kim, Woonghee (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Arif, Muhammad (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Gao, Chunxia (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology,Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
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- Hober, Andreas (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Kotol, David (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Strandberg, Linnéa (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Forsström, Björn (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Sivertsson, Åsa (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Oksvold, Per (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Turkez, Hasan (författare)
- Atatürk Üniversitesi,Atatürk University,Ataturk Univ, Dept Med Biol, Fac Med, TR-25240 Erzurum, Turkey.
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- Grötli, Morten (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology,Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
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- Sato, Yusuke (författare)
- University of Tokyo, Japan,Kyoto University,Kyoto Univ, Inst Adv Study Human Biol WPI ASHBi, Dept Pathol & Tumor Biol, Kyoto 6068501, Japan.;Univ Tokyo, Grad Sch Med, Dept Urol, Tokyo 1138654, Japan.
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- Kume, Haruki (författare)
- University of Tokyo, Japan,Univ Tokyo, Grad Sch Med, Dept Urol, Tokyo 1138654, Japan.
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- Ogawa, Seishi (författare)
- Kyoto University,Karolinska Institutet,Kyoto Univ, Inst Adv Study Human Biol WPI ASHBi, Dept Pathol & Tumor Biol, Kyoto 6068501, Japan.;Karolinska Inst, Dept Med, Ctr Hematol & Regenerat Med, SE-17177 Stockholm, Sweden.
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- Borén, Jan, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Mol & Clin Med, SE-41345 Gothenburg, Sweden.
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- Nielsen, Jens B, 1962 (författare)
- BioInnovation Institute (BII),Chalmers tekniska högskola,Chalmers University of Technology,Chalmers Univ Technol, Dept Biol & Biol Engn, SE-41296 Gothenburg, Sweden.;BioInnovat Inst, DK-2200 Copenhagen N, Denmark.
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- Uhlén, Mathias (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Zhang, Cheng (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab,Zhengzhou Univ, Key Lab Adv Drug Preparat Technol, Sch Pharmaceut Sci, Minist Educ, Zhengzhou 450001, Peoples R China.
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- Mardinoglu, Adil (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab,Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England.
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(creator_code:org_t)
- 2021-01-19
- 2021
- Engelska.
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:2, s. 1-23
- Relaterad länk:
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https://research.cha... (primary) (free)
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https://www.mdpi.com...
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https://doi.org/10.3...
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https://doi.org/10.3...
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https://research.cha...
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https://gup.ub.gu.se...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- PKM
- transcriptomics
- cancer
- alternative splicing
- alternative splicing
- cancer
- PKM
- transcriptomics
- Oncology
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
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Cancers
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- Av författaren/redakt...
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Li, Xiangyu
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Kim, Woonghee
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Arif, Muhammad
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Gao, Chunxia
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Hober, Andreas
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Kotol, David
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visa fler...
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Strandberg, Linn ...
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Forsström, Björn
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Sivertsson, Åsa
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Oksvold, Per
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Turkez, Hasan
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Grötli, Morten
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Sato, Yusuke
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Kume, Haruki
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Ogawa, Seishi
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Borén, Jan, 1963
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Nielsen, Jens B, ...
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Uhlén, Mathias
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Zhang, Cheng
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Mardinoglu, Adil
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinsk biotek ...
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och Medicinsk biotek ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Cancers
- Av lärosätet
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Chalmers tekniska högskola
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Göteborgs universitet
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Kungliga Tekniska Högskolan
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Karolinska Institutet