title: 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.affiliation: Research Genetic Cancer Centre Ltd (R.G.C.C. Ltd), Filotas, Florina, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Apostolou
authors.affiliation: Research Genetic Cancer Centre Ltd (R.G.C.C. Ltd), Filotas, Florina, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Toloudi
authors.affiliation: Research Genetic Cancer Centre Ltd (R.G.C.C. Ltd), Filotas, Florina, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Kourtidou
authors.affiliation: Research Genetic Cancer Centre Ltd (R.G.C.C. Ltd), Filotas, Florina, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Mimikakou
authors.affiliation: Research Genetic Cancer Centre Ltd (R.G.C.C. Ltd), Filotas, Florina, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Vlachou
authors.affiliation: Research Genetic Cancer Centre Ltd (R.G.C.C. Ltd), Filotas, Florina, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Chatziioannou
authors.affiliation: Research Genetic Cancer Centre Ltd (R.G.C.C. Ltd), Filotas, Florina, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Kipourou
authors.affiliation: Research Genetic Cancer Centre Ltd (R.G.C.C. Ltd), Filotas, Florina, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papasotiriou
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D004260:DNA Repair / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D020868:Gene Silencing; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D014411:Neoplastic Stem Cells; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D019895:Transposases / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; C111652:mariner transposases; D011495:Histone-Lysine N-Methyltransferase; C510450:SETMAR protein, human; D019895:Transposases; D004250:DNA Topoisomerases, Type II; D002945:Cisplatin