Open AccessMYC and DNMT 3A‐mediated DNA methylation represses micro RNA ‐200b in triple negative breast cancer
Author(s) -
Pang Yamei,
Liu Jian,
Li Xiang,
Xiao Guodong,
Wang Huangzhen,
Yang Ganghua,
Li Yanbo,
Tang ShouChing,
Qin Sida,
Du Ning,
Zhang Henggang,
Liu Dapeng,
Sun Xin,
Ren Hong
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13916
Subject(s) - triple negative breast cancer , dna methylation , cancer research , gene silencing , microrna , biology , breast cancer , methylation , epigenetics , microbiology and biotechnology , transcription factor , psychological repression , carcinogenesis , cancer , gene expression , gene , genetics
Triple‐negative breast cancer ( TNBC ) is the most aggressive breast cancer subtype with a poor prognosis. The micro RNA ‐200 (miR‐200) family has been associated with breast cancer metastasis. However, the epigenetic mechanisms underlying miR‐200b repression in TNBC are not fully elucidated. In this study, we found that MYC proto‐oncogene, bHLH transcription factor (MYC) and DNA methyltransferase 3A ( DNMT 3A) were highly expressed in TNBC tissues compared with other breast cancer subtypes, while miR‐200b expression was inhibited significantly. We demonstrated that MYC physically interacted with DNMT 3A in MDA ‐ MB ‐231 cells. Furthermore, we demonstrated that MYC recruited DNMT 3A to the miR‐200b promoter, resulting in proximal CpG island hypermethylation and subsequent miR‐200b repression. MiR‐200b directly inhibited DNMT 3A expression and formed a feedback loop in TNBC cells. MiR‐200b overexpression synergistically repressed target genes including zinc‐finger E‐box‐binding homeobox factor 1, Sex determining region Y‐box 2 (SOX2), and CD 133, and inhibited the migration, invasion and mammosphere formation of TNBC cells. Our findings reveal that MYC can collaborate with DNMT 3A on inducing promoter methylation and miR‐200b silencing, and thereby promotes the epithelial to mesenchymal transition and mammosphere formation of TNBC cells.