Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Elgohary, N; Pellegrino, R; Neumann, O; Elzawahry, HM; Saber, MM; Zeeneldin, AA; Geffers, R; Ehemann, V; Schemmer, P; Schirmacher, P; Longerich, T.
Protumorigenic role of Timeless in hepatocellular carcinoma.
Int J Oncol. 2015; 46(2):597-606
Doi: 10.3892/ijo.2014.2751
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- Co-authors Med Uni Graz
- Schemmer Peter
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Aged -
- Carcinogenesis - genetics
- Carcinoma, Hepatocellular - genetics
- Carcinoma, Hepatocellular - pathology
- Cell Cycle Proteins - antagonists & inhibitors
- Cell Cycle Proteins - biosynthesis
- Cell Cycle Proteins - genetics
- Checkpoint Kinase 2 - biosynthesis
- Female -
- Gene Expression Regulation, Neoplastic -
- Humans -
- Intracellular Signaling Peptides and Proteins - antagonists & inhibitors
- Intracellular Signaling Peptides and Proteins - biosynthesis
- Intracellular Signaling Peptides and Proteins - genetics
- Liver Neoplasms - genetics
- Liver Neoplasms - pathology
- Male -
- Middle Aged -
- Peptide Elongation Factor 1 - biosynthesis
- RNA, Small Interfering -
- Find related publications in this database (Keywords)
- circadian clock genes
- oncogene
- hepatocellular carcinoma