miR-486-5p expression is regulated by DNA methylation in osteosarcoma
Namløs, Heidi Maria; Skårn, Magne Nordang; Ali, Deeqa Ahmed Mohamed; Grad, Iwona; Andresen, Kim; Kresse, Stine Henrichson; Munthe, Else; Serra, Massimo; Scotlandi, Katia; Llombart-Bosch, Antonio; Myklebost, Ola; Lind, Guro Elisabeth; Meza, Leonardo Zepeda
Journal article, Peer reviewed
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Date
2022Metadata
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- Department of Clinical Science [2502]
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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.