BoneKEy Reports | BoneKEy Watch
miR-20a facilitates metastasis of osteosarcoma cells to lung tissue
DOI:10.1038/bonekey.2012.76
This study reveals that metastasis of cells from an osteosarcoma to lung tissue occurs when Fas expression on the cells' surface is downregulated, as this allows the cells to remain viable in the normally hostile lung microenvironment. Fas downregulation in osteosarcoma cells seems to be mediated by the action of miRNA within the miR-17–92 cluster. Expression of miRNA from this region shows a strong inverse correlation with Fas expression in tumor cells from patients and in cells from established osteosarcoma cell lines. Furthermore, metastatic LM7 osteosarcoma cells that were stably transfected with anti-miR-20a produced significantly fewer lung metastases compared to control plasmids.
The authors propose that miR-20a lowers Fas expression, allowing the cells to survive the normal clearance mechanisms in the lung that are mediated by FasL, so increasing the metastatic potential of the osteosarcoma cells. Targeting miR-20a could therefore have therapeutic potential.
Editor's comment: The human miR-17–92 cluster encodes 6 miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, and miR-92) and plays a critical role in tumorigenicity. This study shows that miR-20a increases osteosarcoma cell survival in the lung environment, and is the first description linking the miR-17–92 cluster to metastasis formation.
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