title: miR-381 suppresses C/EBPα-dependent Cx43 expression in breast cancer cells.
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.
authors.affiliation: Department of Breast, Thyroid and Pancreas Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China mingjia1001@sina.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Ming
authors.affiliation: Breast Disease Center, the First Affiliated Hospital of The Third Military Medical University, Chongqing, 400038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Breast Disease Center, the First Affiliated Hospital of The Third Military Medical University, Chongqing, 400038, China.
authors.forename: Junze
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Breast, Thyroid and Pancreas Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Shenghao
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Breast, Thyroid and Pancreas Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Pan
authors.affiliation: Department of Breast, Thyroid and Pancreas Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Yinhuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Breast Disease Center, the First Affiliated Hospital of The Third Military Medical University, Chongqing, 400038, China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Fan
authors.affiliation: Breast Disease Center, the First Affiliated Hospital of The Third Military Medical University, Chongqing, 400038, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D018031:Connexin 43 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D018031:Connexin 43; C588249:MIRN381 microRNA, human; D035683:MicroRNAs
keywords: 3′-UTR; C/EBPα; Cx43; MCF-7; MDA-MB-231; miR-381