High expression of ZEB1 correlates with liver metastasis and poor prognosis in colorectal cancer

The First Department of General Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Oncology letters (Impact Factor: 1.55). 02/2013; 5(2):564-568. DOI: 10.3892/ol.2012.1026
Source: PubMed


Zinc finger E-box binding homeobox 1 (ZEB1) has been shown to promote invasion and metastasis in several types of human cancer and to have a prognostic role in certain cancers. However, the clinical significance of ZEB1 in colorectal cancer (CRC) has not been sufficiently investigated. This study aimed to address this issue. In this study, we compared the expression of ZEB1 between CRC tissues and normal adjacent mucosa using quantitative real-time RT-PCR. The association of ZEB1 expression with clinicopathological characteristics was analyzed by appropriate statistical analyses. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the association of ZEB1 expression with survival of patients. The results showed that the relative expression levels of ZEB1 were significantly higher in CRC tissues compared to the normal adjacent mucosa and higher expression of ZEB1 correlated with liver metastasis. Kaplan-Meier analysis indicated that patients with high ZEB1 had a poor overall survival. Moreover, the multivariate analysis showed that high expression of ZEB1 was an independent predictor of overall survival. Our data indicate the potential of ZEB1 as a novel prognostic biomarker for CRC.

Download full-text


Available from: Guangjun Zhang, Jan 30, 2014
  • Source
    • "More importantly, our identified miR-150 target was ZEB1, a member of the zinc finger family of proteins [24]–[26]. ZEB1 is one of the transcriptional inducer in the procedure of epithelial-mesenchymal transition (EMT) in cancer of epithelial origin, such as breast cancer, lung cancer, esophageal squamous cell carcinoma, gastric carcinoma, pancreatic cancer, cervical cancer, endometrial cancer and prostate cancer [23], [27]–[31]. Especially in EOC, Chen et al. [32] reported that downregulating ZEB1 expression with an expression vector-based small hairpin RNA (shRNA) targeting ZEB1 (shZEB1) in EOC SKOV3 cells could inhibit EMT of shZEB1-SKOV3 cells and block shZEB1-SKOV3 cell metastasis in vivo, suggesting its role in enhancing EMT in the EOC cells. They also observed that the shRNA-mediated down-regulation ZEB1 in SKOV3 cells could significantly decrease the tumor growth in the xenograft mice. "
    [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNA (miR)-150 has been reported to be dramatically downregulated in human epithelial ovarian cancer (EOC) tissues and patients' serum compared to normal controls. This study aimed to investigate clinical significance and molecular mechanisms of miR-150 in EOC. In the current study, quantitative real-time PCR analysis showed that miR-150 was significantly downregulated in human EOC tissues compared to normal tissue samples. Then, we demonstrated the significant associations of miR-150 downregulation with aggressive clinicopathological features of EOC patients, including high clinical stage and pathological grade, and shorter overall and progression-free survivals. More importantly, the multivariate analysis identified miR-150 expression as an independent prognostic biomarker in EOC. After that, luciferase reporter assays demonstrated that Zinc Finger E-Box Binding Homeobox 1 (ZEB1), a crucial regulator of epithelial-to-mesenchymal transition (EMT), was a direct target of miR-150 in EOC cells. Moreover, we found that the ectopic expression of miR-150 could efficiently inhibit cell proliferation, invasion and metastasis by suppressing the expression of ZEB1. Furthermore, we also observed a significantly negative correlation between miR-150 and ZEB1 mRNA expression in EOC tissues (rs = -0.45, P<0.001). In conclusion, these findings offer the convincing evidence that aberrant expression of miR-150 may play a role in tumor progression and prognosis in patients with EOC. Moreover, our data reveal that miR-150 may function as a tumor suppressor and modulate EOC cell proliferation, and invasion by directly and negatively regulating ZEB1, implying the re-expression of miR-150 might be a potential therapeutic strategy for EOC.
    Full-text · Article · Aug 2014 · PLoS ONE
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ubiquilin1 (UBQLN1) is a ubiquitin-like domain and a ubiquitin-associated domain containing protein that has been reported to be involved in shuttling proteins to the proteasome, especially during endoplasmic reticulum-associated protein degradation. Thus, UBQLN1 function has been shown to be critical for combating a number of neurological disorders caused by protein aggregation, such as amyotrophic lateral sclerosis, Alzheimer's disease and Huntington's disease. A role for UBQLN1 in regulating processes involved in tumorigenesis has not been demonstrated. Herein, we show that loss of UBQLN1 causes increased cell migration and invasion, actin cytoskeleton reorganization and induction of epithelial-to-mesenchymal transition (EMT). Loss of UBQLN1 results in a significant decrease in the expression of epithelial markers including E-cadherin and claudin1, whereas expression of mesenchymal markers including Vimentin, Snail and ZEB1 are significantly elevated. Interestingly, we found that ZEB1 is required for induction of mesenchymal-like properties following loss of UBQLN1 and ZEB1 is capable of repressing expression of UBQLN1, suggesting a physiological, reciprocal regulation of EMT by UBQLN1 and ZEB1. Further, we find evidence for a role for UBQLN2 in also regulating EMT and cell migration. These observations have potential clinical relevance because the UBQLN1 gene is lost and underexpressed in a large percentage of human cancer cell lines, and primary human lung cancer samples and recurrent mutations in all five UBQLN family members have been identified in human lung cancers. Taken together, our results suggest for the first time a role for UBQLN family members in cancer biology.Oncogene advance online publication, 21 April 2014; doi:10.1038/onc.2014.97.
    Full-text · Article · Apr 2014 · Oncogene
  • [Show abstract] [Hide abstract]
    ABSTRACT: Zinc finger E-box binding homeobox factor 1 (ZEB1), as a crucial mediator of "epithelial-mesenchymal transition," contributes to malignant progression of various epithelial tumors. However, its involvement in human esophageal squamous cell carcinoma (ESCC) remains unclear. In order to investigate the expression pattern of ZEB1 in ESCC tissues and evaluate its associations with tumor progression and patients' prognosis, 100 pairs of formalin-fixed and paraffin-embedded cancerous and adjacent noncancerous tissues from patients with ESCC were used to detect the expression pattern of ZEB1 by immunohistochemistry. Then, the association between ZEB1 expression, clinicopathological parameters, and prognosis of ESCC was examined. We also performed migration and invasion assays of small interfering RNA (siRNA)-targeted ZEB1-transfected cells in vitro. As a result, expression level of ZEB1 was significantly higher in ESCC tissues compared to that in adjacent noncancerous tissues (P < 0.001). High expression of ZEB1 was observed in 55.00 % (55/100) of ESCCs. In addition, high ZEB1 expression was found to be closely correlated with advanced tumor stage (P = 0.001), positive lymph node metastasis (P = 0.001), great tumor depth (P = 0.03), and high histologic grade (P = 0.008). Moreover, multivariate analysis showed that the status of ZEB1 expression was an independent predictor for overall survival in ESCC. Furthermore, knockdown of ZEB1 by transfection of siRNA-ZEB1 abrogated the migration and invasion of ESCC cells in vitro. Taken together, our data offer the convincing evidence that ZEB1 may play a crucial role in promoting aggressive ESCC progression. ZEB1 may serve as an effective prognostic marker and a potential target for therapeutic intervention of ESCC.
    No preview · Article · Aug 2014 · Tumor Biology
Show more