Potential role for the Metnase transposase fusion gene in colon cancer through the regulation of key genes.

Abstract

The Metnase fusion gene consists of a SET histone methyltransferase domain and a transposase domain from Mariner transposase. This transposable element is involved in chromosome decatenation, enhances DNA repair, promotes foreign DNA integration, and assists topoisomerase II function. This study investigates the role of Metnase in colon cancer homeostasis and maintenance of the stemness phenotype in colon cancer stem cells (CSCs). Silencing of Metnase was performed in human cancer cell lines before and after treatment with cisplatin, and in colon CSCs. Subsequent changes in the expression of genes involved in repair mechanisms, DNA synthesis, topoisomerase II function, and metastasis as well stemness transcription factors were studied with RT-qPCR experiments. Cellular viability and apoptosis were evaluated by flow cytometry. The results suggest that Metnase influences the expression of many genes involved in the above processes. Furthermore, Metnase levels appear to impact upon expression of NANOG, OCT3/4, and SOX2. Suppression of Metnase also led to an increase in apoptosis. Therefore, Metnase may possess an important role in DNA repair, topoisomerase II function, and the maintenance of stemness during colon cancer development.

• Authors: Panagiotis Apostolou, Maria Toloudi, Eleni Kourtidou, Georgia Mimikakou, Ioanna Vlachou, Marina Chatziioannou, Vasiliki Kipourou, Ioannis Papasotiriou
• Journal: PloS one (PLoS One) Vol. 9 Issue 10 Pg. e109741 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25333365 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Oncogene Proteins, Fusion
• mariner transposases
• Histone-Lysine N-Methyltransferase
• SETMAR protein, human
• Transposases
• DNA Topoisomerases, Type II
• Cisplatin

Topics

• Apoptosis (drug effects, genetics)
• Cell Line, Tumor
• Cell Survival (drug effects, genetics)
• Cisplatin (pharmacology)
• Colonic Neoplasms (genetics, pathology)
• DNA Repair (drug effects)
• DNA Topoisomerases, Type II (genetics)
• DNA-Binding Proteins (genetics)
• Gene Expression Regulation, Neoplastic (drug effects, genetics)
• Gene Silencing
• Histone-Lysine N-Methyltransferase (genetics)
• Humans
• Neoplastic Stem Cells
• Oncogene Proteins, Fusion (genetics)
• Transposases (genetics)