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. These in vitro results 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.

Liraglutide inhibits the proliferation and promotes the apoptosis of MCF-7 human breast cancer cells through downregulation of microRNA-27a expression

“…3I and J . Previous studies have also included the use of a common control for mimics and inhibitor experiments ( 28 , 29 ).…”

Development and Validation of a 6-miRNA Prognostic Signature in Spinal Chordoma

“…In addition, published data have suggested that many other miRNAs may impact patient outcomes in spinal chordoma (7). Our future study will further evaluate the eligibility for adding other miRNAs (such as miR-219-5p and miR-31) into the miRscore model and assessed their effect on spinal chordoma prognosis (45,46). Finally, our study is a correlation study in nature.…”

The Current Understanding of MicroRNA’s Therapeutic, Diagnostic, and Prognostic Role in Chordomas: A Review of the Literature

“…Besides the miRNAs described above, numerous others have been reported to be associated with the pathogenesis of chordoma. For example, Bayrak et al report an additional 53 dysregulated miRNAs in skull base chordoma compared to the biology of normal nucleus pulposus, and Wei et al demonstrate the chordomagenic effect of miRNA 219-5p expression and its association with poor prognosis by studying spinal and sacral chordomas [4,17].…”

“…Bayrak et al and Zou et al look at skull base and spinal chordomas [4,12,18]. Wei et al study both spinal and sacral chordomas [17]. Although miRNA 155 upregulation was studied to be associated with poorer prognosis of sacral chordoma by Osaka et al, an isolated study of the sacral chordoma’s molecular pathogenesis i.e., identification of certain miRNAs’ association with a specific oncogene, is lacking [8].…”