title: The potential function of microRNA in chordomas.
abstract: Little is known about the molecular biology of chordomas, which are rare, chemoresistant tumors with no well-established treatment. miRNAs regulate gene networks and pathways. We aimed to evaluate the effects of dysregulated miRNA in chordomas would help reveal the underlying mechanisms of chordoma initiation and progression. In this study, miR-31, anti-miR-140-3p, anti-miR148a, and miR-222 were transiently transfected to chordoma cell lines and an MTS assay, apoptosis assay, and cell-cycle analysis were conducted to evaluate the effects. The mRNA level of predicted and confirmed targets of each miRNA, as well as the EMT and MET markers of U-CH1 and MUG-Chor1, were assessed with real-time polymerase chain reaction. Transient transfection of miRNA mimics was achieved, as each mimic increased or decreased the level of its corresponding miRNA. miR-31 decreased cell viability in MUG-Chor1 and U-CH2 after 72h, which is consistent with previous findings for U-CH1. Both miR-31 and anti-miR-148a induced apoptosis in all three cell lines. Although each miRNA had a similar pattern, miR-31 had the most effective S-phase arrest in all three cell lines. RDX, MET, DNMT1, DNMT3B, TRPS1, BIRC5, and KIT were found to be targeted by the selected miRNAs. The level of miR-222 in chordoma cell lines U-CH1 and MUG-Chor1 correlated positively with EMT markers and negatively with MET markers. This study uncovered the potential of miR-31, miR-140-3p, miR-148a, and miR-222-3p to be key molecules in the cell viability, cell cycle, and apoptosis in chordomas, as well as initiation, differentiation, and progression.
authors.affiliation: Department of Medical Genetics, Yeditepe University Medical School, Inonu Mah Kayisdagi Cad. 26 Agustos Yerlesimi, 34755 Atasehir, Istanbul, Turkey; Department of Biotechnology, Institute of Science Yeditepe University, Inonu Mah. Kayisdagi Cad. 26 Agustos Yerlesimi, 34755 Atasehir, Istanbul, Turkey. Electronic address: sgulluoglu@gmail.com.
authors.forename: Sukru
authors.initials: S
authors.lastname: Gulluoglu
authors.affiliation: Department of Biotechnology, Institute of Science Yeditepe University, Inonu Mah. Kayisdagi Cad. 26 Agustos Yerlesimi, 34755 Atasehir, Istanbul, Turkey. Electronic address: tuysuzemrecan@gmail.com.
authors.forename: Emre Can
authors.initials: EC
authors.lastname: Tuysuz
authors.affiliation: Department of Medical Genetics, Yeditepe University Medical School, Inonu Mah Kayisdagi Cad. 26 Agustos Yerlesimi, 34755 Atasehir, Istanbul, Turkey. Electronic address: aysegul.kuskucu@yeditepe.edu.tr.
authors.forename: Aysegul
authors.initials: A
authors.lastname: Kuskucu
authors.affiliation: Department of Neurosurgery, Yeditepe University Hospital, Icerenkoy Mah Hastane Yolu Sok., 102-104, 34755 Atasehir, Istanbul, Turkey. Electronic address: drture@yahoo.com.
authors.forename: Ugur
authors.initials: U
authors.lastname: Ture
authors.affiliation: Department of Neurosurgery, Yeditepe University Hospital, Icerenkoy Mah Hastane Yolu Sok., 102-104, 34755 Atasehir, Istanbul, Turkey. Electronic address: batalay@yeditepe.edu.tr.
authors.forename: Basar
authors.initials: B
authors.lastname: Atalay
authors.affiliation: Department of Biotechnology, Institute of Science Yeditepe University, Inonu Mah. Kayisdagi Cad. 26 Agustos Yerlesimi, 34755 Atasehir, Istanbul, Turkey. Electronic address: fsahin@yeditepe.edu.tr.
authors.forename: Fikrettin
authors.initials: F
authors.lastname: Sahin
authors.affiliation: Department of Medical Genetics, Yeditepe University Medical School, Inonu Mah Kayisdagi Cad. 26 Agustos Yerlesimi, 34755 Atasehir, Istanbul, Turkey. Electronic address: ofbayrak@yeditepe.edu.tr.
authors.forename: Omer Faruk
authors.initials: OF
authors.lastname: Bayrak
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival; D002817:Chordoma / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000235:genetics / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D009841:Oligonucleotides; C550570:MIRN148 microRNA, human; C525710:MIR222, human; C534612:MIRN31 microRNA, human; C544302:Mirn140 microRNA, human
keywords: EMT; KIT; Microarray; TRPS1; Target; miR-222