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- Title
miR-381 suppresses C/EBPα-dependent Cx43 expression in breast cancer cells.
- Authors
Jia Ming; Yan Zhou; Junze Du; Shenghao Fan; Beibei Pan; Yinhuan Wang; Lingjun Fan; Jun Jiang
- Abstract
Cx43 (connexin43) is an enhancer of the metastasis of breast cancer cells. Our previous study identified miR-381 as an indirect suppressor of Cx43 gene expression, with the precise mechanism being not understood. In the present study, using a reporter gene assay, we found that miR-381 suppressed Cx43 gene expression via the promoter region -500/-250. With site-directed gene mutation, we demonstrated that miR-381 could directly bind with the sequences CACUUGUAU in the 3'-UTR so as to inhibit C/EBPα (CCAAT/enhancer-binding protein α) expression. C/EBPα was further identified as a novel transcription factor by binding to a canonic element (AATTGTC) locating at -459/-453 in the promoter region of the Cx43 gene. Functionally, we demonstrated that miR-381 suppressed C/EBPα- and Cx43-dependent migration and invasion of breast cancer cells. Finally, we revealed that decreased levels of miR-381 as well as increased expression of C/EBPα and Cx43 in the metastatic breast cancer cells and tissues. Therefore we are the first to identify that miR-381 suppresses C/EBPα-dependent Cx43 expression in breast cancer cells. The miR-381-C/EBPα-Cx43 axis might be a useful diagnostic and therapeutic target of metastatic breast cancer.
- Subjects
BREAST cancer gene therapy; MICRORNA; CONNEXIN 43; CCAAT enhancer binding proteins; TRANSCRIPTION factors; SITE-specific mutagenesis
- Publication
Bioscience Reports, 2015, Vol 35, Issue 6, p1
- ISSN
0144-8463
- Publication type
Article
- DOI
10.1042/BSR20150167