miR-486-5p expression is regulated by DNA methylation in osteosarcoma

Author:

Namløs Heidi M.,Skårn Magne,Ahmed Deeqa,Grad Iwona,Andresen Kim,Kresse Stine H.,Munthe Else,Serra Massimo,Scotlandi Katia,Llombart-Bosch Antonio,Myklebost Ola,Lind Guro E.,Meza-Zepeda Leonardo A.

Abstract

Abstract Background Osteosarcoma is the most common primary malignant tumour of bone occurring in children and young adolescents and is characterised by complex genetic and epigenetic changes. The miRNA miR-486-5p has been shown to be downregulated in osteosarcoma and in cancer in general. Results To investigate if the mir-486 locus is epigenetically regulated, we integrated DNA methylation and miR-486-5p expression data using cohorts of osteosarcoma cell lines and patient samples. A CpG island in the promoter of the ANK1 host gene of mir-486 was shown to be highly methylated in osteosarcoma cell lines as determined by methylation-specific PCR and direct bisulfite sequencing. High methylation levels were seen for osteosarcoma patient samples, xenografts and cell lines based on quantitative methylation-specific PCR. 5-Aza-2′-deoxycytidine treatment of osteosarcoma cell lines caused induction of miR-486-5p and ANK1, indicating common epigenetic regulation in osteosarcoma cell lines. When overexpressed, miR-486-5p affected cell morphology. Conclusions miR-486-5p represents a highly cancer relevant, epigenetically regulated miRNA in osteosarcoma, and this knowledge contributes to the understanding of osteosarcoma biology.

Publisher

Springer Science and Business Media LLC

Subject

Genetics,Biotechnology

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