Identification of miR-200a as a novel suppressor of connexin 43 in breast cancer cells

Both microRNAs (miRs) and Connexin 43 (Cx43) were important regulators of the metastasis of breast cancer, while the miRs regulating Cx43 expression in breast cancer cells were still obscure. Here we scanned and found miR-1, miR-206, miR-200a, miR-381, miR-23a/b and miR-186 were functional suppressors of human Cx43 mRNA and protein expression. Specially, we demonstrated that only miR-200a could directly target the 3’-untranslated region (3’-UTR) of human Cx43 gene. Functionally, overexpression of Cx43 in MCF-7 cells potentiated the migration activity, while additional miR-200a treatment notably prevented this effect. Finally, we demonstrated that decreased levels of miR-200a and elevated expression of Cx43 in the metastatic breast cancer tissues versus the primary ones. Thus, we are the first to identify miR-200a as a novel and direct suppressor of human Cx43, indicating that miR200a/Cx43 axis might be a useful diagnostic and therapeutic target of metastatic breast cancer.