Regulation of TRIB3 mRNA and protein in breast cancer

• Published in: PloS one Vol. 7; no. 11; p. e49439
• Main Authors: Wennemers, Marloes, Bussink, Johan, van den Beucken, Twan, Sweep, Fred C G J, Span, Paul N
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.11.2012; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Anoxia; Apoptosis; Autophagy; Biology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cancer; Cell cycle; Cell Cycle Proteins - biosynthesis; Cell Line, Tumor; Cell survival; Disease Progression; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genomes; Homology; Humans; Hypoxia; Kinases; Laboratories; Medical prognosis; Medicine; Messenger RNA; MicroRNA; MicroRNAs; MicroRNAs - metabolism; Middle Aged; miRNA; Oncology; Patients; Prognosis; Protein expression; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - biosynthesis; Proteins; Proteins - chemistry; Repressor Proteins - biosynthesis; Ribonucleic acid; RNA; RNA, Messenger - metabolism; RNA, Small Interfering - metabolism; Rodents; Studies; Time Factors; Transcription; Translation; Translation (Genetics); Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0049439

Tribbles homolog 3 (TRIB3) is a scaffold protein activated under hypoxic conditions and involved in several cell survival and proliferation pathways. Recently, we reported opposite associations of TRIB3 mRNA and protein with breast cancer prognosis. In this study, we investigated this discrepancy between TRIB3 mRNA and protein in human breast cancer. We provide several lines of evidence demonstrating that TRIB3 is a stabile protein which levels are not controlled by rapid protein breakdown. Interestingly, we were able to show that during anoxia TRIB3 mRNA translation was profoundly inhibited. Hypoxia induced micro RNA 24 was not responsible for the translational repression of TRIB3. Furthermore miRNA-24 expression levels in breast cancer patient specimens showed no correlation with TRIB3 mRNA or TRIB3 protein levels, or with prognosis. Thus, the expression of miRNA-24 does not explain the difference between mRNA and protein expression of TRIB3 in this cohort of breast cancer patients. In conclusion, TRIB3 protein is a stable protein which levels are predominantly regulated by translational control of TRIB3 mRNA transcript.