title: miR-219-5p inhibits proliferation and clonogenicity in chordoma cells and is associated with tumor recurrence.
abstract: Chordoma is a rare malignant bone tumor that is usually localized to the skull base, vertebral column and sacrum. The transcription factor brachyury, which is encoded by the T gene, has a critical role in the development and progression of chordoma, although the mechanisms underlying brachyury regulation remain unclear. The aim of the current study was to identify and characterize microRNAs (miRs) that regulate brachyury expression in chordoma. MicroRNAs that target brachyury were predicted using miRanda and TargetScan. Using reverse transcription-quantitative polymerase chain reaction, miR-219-5p was shown to be significantly downregulated in chordoma tissues and the U-CH2 chordoma cell lines. A dual-luciferase reporter assay was used to validate the inhibitory effect of miR-219-5p on brachyury mRNA expression. The expression level of brachyury was downregulated in U-CH2 cells following transfection with miR-219-5p mimics and upregulated following transfection with the miR-219-5p inhibitor. The effects of miR-219-5p on the proliferation and clonogenicity of chordoma cells were assessed using cell counting kit-8, EdU and clone formation assays. Thesein vitroresults indicated that miR-219-5p may have an important role in regulating the cell proliferation and clonogenicity of human chordoma cells, potentially by targeting brachyury. Furthermore, the associations between the expression levels of miR-219-5p and various clinicopathological factors were analyzed, and miR-219-5p expression was shown to correlate with tumor extent and recurrence. These results suggested that miR-219-5p functions as a tumor suppressor in chordoma and, therefore, that miR-219-50 may be a potential target for therapeutic intervention.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Skull Base Surgery Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Skull Base Surgery Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors.forename: Qiuhang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Skull Base Surgery Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Skull Base Surgery Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Skull Base Surgery Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Skull Base Surgery Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, P.R. China.
authors.forename: Pu
authors.initials: P
authors.lastname: Li
keywords: brachyury; chordoma; clonogenicity; miR-219-5p; proliferation; recurrence