Enforced expression of miR-205 was shown to inhibit cell invasion and suppress lung metastasis of breast cancer cells in nude mice, possibly through targeting ErbB3 [35]. MiR-205 also exerts inhibitory effects on cellular invasiveness and migration http://www.selleckchem.com/products/Pazopanib-Hydrochloride.html in prostate cancer and glioblastoma cells, through down-regulation of the protein kinase C�� and low-density lipoprotein receptor-related protein 1, respectively [36,37]. Using miR target prediction algorithms, ErB3, E2F1, E2F5, ZEB1, ZEB2, and protein kinase C�� have been indentified as putative miR-205 targets [36]. In the present study, knockdown of miR-205 expression substantially enhanced cellular expression of ZEB2 in ESCC cells. In fact, previous and present studies employing a reporter gene assay confirmed miR-205 binding to the ZEB2 3′-UTR [15,17].

Although the ESCC cells examined in this study did not express ZEB1 sufficiently, direct interaction of miR-205 with ZEB1 3′-UTR was shown in other cell types but not in ESCC cells examined in this study [15,17]. ZEB1 and ZEB2 are related homeodomain-containing transcriptional factors that repress E-cadherin transcription [17,38,39]. E-cadherin is a central component of the adherens junction complex responsible for cell-cell adhesion and maintenance of cytoskeleton organization [15]. It is known that loss of E-cadherin expression is a key event in the EMT, which can be recapitulated during tumor progression, constituting an early step in tumor metastasis including ESCC [15,40-43].

In line with this, cellular E-cadherin expression was substantially reduced, whereas N-cadherin expression emerged in ESCC cells transfected with anti-miR-205 inhibitor to suppress ZEB2, and they were endowed with properties allowing augmented invasion through EMT. Gregory et al described that the miRNA-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429), as well as miR-205, was markedly downregulated in breast and colon cancer cells that had undergone EMT [15]. Collectively, miR-205, along with members of the miR-200 family, can be a key regulator of EMT to widely enforce the indolent epithelial-like phenotype, not limited to ESCC. In clinical settings, lower levels of miR-205 were significantly associated with loco-regional recurrence and poor survival of patients with head and neck squamous cell carcinoma [41].

Further studies are warranted to assess whether miR-205 expression levels could be a predictive biomarker for clinical outcomes in ESCC. Conclusions MiR-205 expression was specifically increased in ESCC cells. Brefeldin_A MiR-205 is likely to control cell invasion and migration in ESCC cells through its repression of ZEB2, a repressor of E-cadherin. These findings establish the tumor-suppressive role of miR-205, which may serve as a unique therapeutic target for ESCC. Competing interests The authors declare that they have no competing interests.