Methylation‐regulated miR‐149 modulates chemoresistance by targeting Glc NA c N ‐deacetylase/ N ‐sulfotransferase‐1 in human breast cancer

Dysregulation of micro RNA is strongly implicated in the chemoresistance of cancer. In this study, we found that miR‐149 was downregulated and involved in chemoresistance in adriamycin ( ADM )‐resistant human breast cancer cells ( MCF ‐7/ ADM ). Downregulation of miR‐149 was related to hypermethylation of its 5′‐ UTR ; this methylation also affected the expression of the glypican 1 gene, which is both the host and the target gene of miR‐149. Furthermore, we found that miR‐149 modulated chemoresistance through targeting the expression of Glc NA c N ‐deacetylase/ N ‐sulfotransferase‐1 ( NDST 1). With downregulated miR‐149, NDST 1 expression was increased in chemoresistant MCF ‐7/ ADM cells versus control MCF ‐7 wild‐type cells. The increased NDST 1 then activated a heparan sulfate‐related pathway involving activation of heparanase. Finally, expression of miR‐149 and NDST 1 was confirmed in clinical chemoresistant samples of breast cancers receiving anthracycline/taxane‐based chemotherapies. The high expression of NDST 1 was also an unfavorable predictor for distant relapse‐free survival in Her2 and basal breast cancers. Taken together, our findings demonstrate that miR‐149 is regulated by methylation, and is a modulator of cancer chemoresistance by targeting NDST 1 .