MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells

Abstract

BackgroundEsophageal squamous cell carcinoma (ESCC) is often diagnosed at later stages until they are incurable. MicroRNA (miR) is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC.MethodsTotal RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT)-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR.ResultsBased on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold) in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2, accompanied by reduction of E-cadherin, a regulator of epithelial mesenchymal transition. The miR-205 expression levels were not associated with histological differentiation of human ESCC.ConclusionsThese results imply that miR-205 is an ESCC-specific miR that exerts tumor-suppressive activities with EMT inhibition by targeting ZEB2.

Metformin lowers the threshold for stress-induced senescence: A role for the microRNA-200 family and miR-205

“…Cellular senescence should be viewed as a general cellular stress response program that can be activated by the cell when coordinately exerts tumor-suppressor activities with the miR-200 family to inhibit EMT, 72,[78][79][80] was also markedly upregulated in HDFs that have undergone SIS in response to metformin (Fig. 4A).…”

Loss of microRNA-205 expression is associated with melanoma progression

“…Given the well-described role of miR-205 in EMT pathways, [34][35][36] we investigated the effects of miR-205 overexpression on EMT family members and demonstrated a connection between miR-205 overexpression and an associated reduction of ZEB2 mRNA and protein levels with a reciprocal increase on E-cadherin mRNA and protein levels. Re-introduction of ZEB2 into 1205Lu melanoma cells overexpressing miR-205 rescues the observed defects in cell migration and invasion and restores suppression of E-cadherin.…”

“…[34][35][36] As miR-205 expression is progressively diminished from nevi to primary melanomas to metastatic melanomas and because enforced expression of miR-205 impairs melanoma cell mobility, we hypothesized that miR-205 expression might impact ZEB1/2 and consequently, E-cadherin expression in melanoma cells. As shown in Figure 5a, we established a panel of cell lines representing all stages of melanoma progression: WM35 (radial growth phase only), WM793 (vertical growth phase primary melanoma), WM115A (metastatic melanoma) and 1205Lu (metastatic melanoma) stably expressing relatively similar levels of (Figure 5a).…”

MicroRNA-205 Directly Regulates the Tumor Suppressor, Interleukin-24, in Human KB Oral Cancer Cells

“…As another mechanism of tumor suppression by miR-205, Dar et al (2011) reported that miR-205 suppressed cell proliferation by regulating the E2F1 protein in melanoma cells. In addition, Matsushima et al (2011) examined the role of miR-205 in inhibiting cellular invasion and migration in esophageal squamous carcinoma. Interestingly, Majid et al (2010) showed that a new functional mechanism of miR-205 specifically activates tumor suppressor genes, such as interleukin-24 (IL-24) and interleukin-32 (IL-32), by targeting specific sites in their promoters.…”