2.50
Hdl Handle:
http://hdl.handle.net/10033/606082
Title:
Protumorigenic role of Timeless in hepatocellular carcinoma.
Authors:
Elgohary, Nahla; Pellegrino, Rossella; Neumann, Olaf; Elzawahry, Heba M; Saber, Magdy M; Zeeneldin, Ahmed A; Geffers, Robert ( 0000-0003-4409-016X ) ; Ehemann, Volker; Schemmer, Peter; Schirmacher, Peter; Longerich, Thomas
Abstract:
The mammalian timeless (TIM) protein interacts with proteins of the endogenous clock and essentially contributes to the circadian rhythm. In addition, TIM is involved in maintenance of chromosome integrity, growth control and development. Thus, we hypothesized that TIM may exert a potential protumorigenic function in human hepatocarcinogenesis. TIM was overexpressed in a subset of human HCCs both at the mRNA and the protein level. siRNA-mediated knockdown of TIM reduced cell viability due to the induction of apoptosis and G2 arrest. The latter was mediated via CHEK2 phosphorylation. In addition, siRNA-treated cells showed a significantly reduced migratory capacity and reduced expression levels of various proteins. Mechanistically, TIM directly interacts with the eukaryotic elongation factor 1A2 (EEF1A2), which binds to actin filaments to promote tumor cell migration. siRNA-mediated knockdown of TIM reduced EEF1A2 protein levels thereby affecting ribosomal protein biosynthesis. Thus, overexpression of TIM exerts oncogenic function in human HCCs, which is mediated via CHEK2 and EEF1A2.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Protumorigenic role of Timeless in hepatocellular carcinoma. 2015, 46 (2):597-606 Int. J. Oncol.
Journal:
International journal of oncology
Issue Date:
Feb-2015
URI:
http://hdl.handle.net/10033/606082
DOI:
10.3892/ijo.2014.2751
PubMed ID:
25405317
Type:
Article
Language:
en
ISSN:
1791-2423
Appears in Collections:
publications of the research group genomeanalytics (GMAK)

Full metadata record

DC FieldValue Language
dc.contributor.authorElgohary, Nahlaen
dc.contributor.authorPellegrino, Rossellaen
dc.contributor.authorNeumann, Olafen
dc.contributor.authorElzawahry, Heba Men
dc.contributor.authorSaber, Magdy Men
dc.contributor.authorZeeneldin, Ahmed Aen
dc.contributor.authorGeffers, Roberten
dc.contributor.authorEhemann, Volkeren
dc.contributor.authorSchemmer, Peteren
dc.contributor.authorSchirmacher, Peteren
dc.contributor.authorLongerich, Thomasen
dc.date.accessioned2016-04-20T14:03:46Zen
dc.date.available2016-04-20T14:03:46Zen
dc.date.issued2015-02en
dc.identifier.citationProtumorigenic role of Timeless in hepatocellular carcinoma. 2015, 46 (2):597-606 Int. J. Oncol.en
dc.identifier.issn1791-2423en
dc.identifier.pmid25405317en
dc.identifier.doi10.3892/ijo.2014.2751en
dc.identifier.urihttp://hdl.handle.net/10033/606082en
dc.description.abstractThe mammalian timeless (TIM) protein interacts with proteins of the endogenous clock and essentially contributes to the circadian rhythm. In addition, TIM is involved in maintenance of chromosome integrity, growth control and development. Thus, we hypothesized that TIM may exert a potential protumorigenic function in human hepatocarcinogenesis. TIM was overexpressed in a subset of human HCCs both at the mRNA and the protein level. siRNA-mediated knockdown of TIM reduced cell viability due to the induction of apoptosis and G2 arrest. The latter was mediated via CHEK2 phosphorylation. In addition, siRNA-treated cells showed a significantly reduced migratory capacity and reduced expression levels of various proteins. Mechanistically, TIM directly interacts with the eukaryotic elongation factor 1A2 (EEF1A2), which binds to actin filaments to promote tumor cell migration. siRNA-mediated knockdown of TIM reduced EEF1A2 protein levels thereby affecting ribosomal protein biosynthesis. Thus, overexpression of TIM exerts oncogenic function in human HCCs, which is mediated via CHEK2 and EEF1A2.en
dc.language.isoenen
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshCarcinogenesisen
dc.subject.meshCarcinoma, Hepatocellularen
dc.subject.meshCell Cycle Proteinsen
dc.subject.meshCheckpoint Kinase 2en
dc.subject.meshFemaleen
dc.subject.meshGene Expression Regulation, Neoplasticen
dc.subject.meshHumansen
dc.subject.meshIntracellular Signaling Peptides and Proteinsen
dc.subject.meshLiver Neoplasmsen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshPeptide Elongation Factor 1en
dc.subject.meshRNA, Small Interferingen
dc.titleProtumorigenic role of Timeless in hepatocellular carcinoma.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalInternational journal of oncologyen

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