Abstract
Runt-related transcription factor 3 (RUNX3) is a tumor suppressor gene whose reduced expression may play an important role in the development and progression of esophageal squamous cell cancer (ESCC). The aim of this study was to investigate the clinical relevance of RUNX3 in ESCC patients and effects of overexpression on biological behaviour of Eca109 cells in vitro and in vivo. Immunohistochemistry was performed to detect the clinical relevance of RUNX3 and lymph node metastasis in 80 ESCC tissues and 40 non-cancerous tissues using the SP method. RT-PCR and Western blotting were applied to assess the RUNX3 level and verify the Eca109 cell line with stable overexpression. Localization of RUNX3 proteins was performed by cell immunofluorescence. CCK-8 and Scrape motility assays were used to determine proliferation and migration and the TUNEL assay to analyze cell apoptosis. Invasive potential was assessed in cell transwell invasion experiments. In nude mice, tumorigenesis in vivo was determined. Results showed decreased expression of RUNX3 in esophageal tissue to be significantly related to lymph node metastasis (LNM) (P<0.01). In addition, construction of a recombinant lentiviral vector and transfection into the human ESCC cell line Eca109 demonstrated that overexpression could inhibit cell proliferation, migration and invasion, and induce apoptosis. The in vivo experiments in mice showed tumorigenicity and invasiveness to be significantly reduced. Taken together, our studies indicate that underexpression of RUNX3 in human ESCC tissue is significantly correlated with progression. Restoration of RUNX3 expression significantly inhibits ESCC cells proliferation, migration, invasion and tumorigenesis.
Highlights
Esophageal squamous cell cancer (ESCC) is a malignancy that arises from esophageal epithelial cells, it is a potentially fatal disease with high incidence worldwide, in China (Sun et al, 2011)
We focus on the correlation between RUNX3 expression and lymph node metastasis (LNM), detection the inhibit effects of RUNX3 overexpression in esophageal squamous cell cancer (ESCC) cells biological behaviour and tumorigenesis, aimed to identify a new therapeutic target and provide a foundation for gene therapy in esophageal cancer
RUNX3 is located on human chromosome region 1p36 and plays an important role in the transforming growth factor (TGF)-β signaling pathway (Bangsow et al, 2001)
Summary
Esophageal squamous cell cancer (ESCC) is a malignancy that arises from esophageal epithelial cells, it is a potentially fatal disease with high incidence worldwide, in China (Sun et al, 2011). Despite technical progress for ESCC, the effect of treatment is still unsatisfactory. ESCC is still a leading cause of cancer-related death (Dresner and Griffin., 2000). It is of great clinical value to find new genes involved in ESCC tumorigenesis and progression, in order to develop early diagnosis and improved disease outcome predication following treatment of this dangerous disease (Subramaniam et al, 2009). Multiple genes participate in the occurrence and development of ESCC. Runt-related transcription factor 3 (RUNX3) is one of the runt-domain family of transcription factors which has been first reported in gastric cancer. The RUNX3 gene is regarded as a tumor suppressor gene in many human tumors, and its inactivation is believed to be related with the occurrence and development of tumor (Ito et al, 2008). Previous study demonstrated that the down-regulation of Runx in ESCC tissues is associated with poor prognosis (Soong et al, 2009)
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