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

Autor: Heidi M. Namløs, Magne Skårn, Deeqa Ahmed, Iwona Grad, Kim Andresen, Stine H. Kresse, Else Munthe, Massimo Serra, Katia Scotlandi, Antonio Llombart-Bosch, Ola Myklebost, Guro E. Lind, Leonardo A. Meza-Zepeda
Rok vydání: 2021
Předmět:
Zdroj: BMC Genomics
ISSN: 1471-2164
Popis: 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.
Databáze: OpenAIRE