Although mounting evidence indicates the involvement of galectin-3 in cancer progression and metastasis, the underlying molecular mechanisms remain largely unknown. In this study, we investigated the effect and possible mechanism of galectin-3 on the migration and invasion of B16F10, a metastatic melanoma cell line, in which galectin-3 and matrix metalloproteinase-1 (MMP-1) were both found to be highly expressed. Knockdown of galectin-3 with specific siRNA reduced migration and invasion, which was associated with reduced expression of MMP-1. To further investigate the underlying mechanism, we examined the effect of galectin-3 knockdown on the activity of AP-1, a transcriptional factor regulating MMP-1 expression. We found that galectin-3 directly interacted with AP-1 and facilitated the binding of this complex to the MMP-1 promoter that drives MMP-1 transcription. Moreover, silencing of galectin-3 inhibited binding of fra-1 and c-Jun to promoter sites of MMP-1 gene. Consistent with these in vitro findings, our in vivo study demonstrated that galectin-3 shRNA treatment significantly reduced the total number of mouse lung metastatic nodules. Taken together, galectin-3 facilitates cell migration and invasion in melanoma in vitro and can induce metastasis in vivo, in part through, regulating the transcription activity of AP-1 and thereby up-regulating MMP-1 expression.

Promoter methylation may play an important role in the epigenetic silencing of RIZ1 gene expression in human ESCC. RIZ1 is considered to be a potential tumor suppressor gene and may be a biological parameter for testing early stage human ESCC.

The present study aimed to investigate the expression and role of SET and MYND domain-containing protein 3 (SMYD3) in esophageal squamous cell carcinoma; to observe the proliferation of esophageal squamous cell carcinoma after suppression of SMYD3 expression; and to explore the effect of SMYD3 downregulation on the expression of retinoblastoma protein-interacting zinc finger gene 1 (RIZ1). Tissues from 11 patients, including cancer and normal esophageal tissues, were obtained by surgery to observe the SMYD3 protein expression immunohistochemistry. Esophageal squamous cell carcinoma TE13 cells were transfected with four different SMYD3-shRNA plasmids, and SMYD3 mRNA expression levels were assessed to select the most efficient interfering plasmid. After SMYD3 downregulation in TE13 cells, mRNA and protein expression levels of SMYD3 and RIZ1 were determined using RT-PCR and western blotting, and cell proliferation was evaluated by the MTT method. In all 11 tissue paired samples, SMYD3 protein expression was higher in the cancer tissues (72.7%; 8/11), than that in the normal tissues (18.2%; 2/11) (Fisher's exact test, P=0.03). The mRNA expression levels of SMYD3 were significantly decreased by RNA interference (P<0.05), and plasmid SMYD3-shRNA-1242 was determined to be the most effective. Compared with the controls, transfection with the SMYD3-shRNA interfering plasmid significantly reduced the SMYD3 mRNA and protein expression levels in TE13 cells (P<0.05), whereas the expression levels of the anti-oncogene RIZ1 were increased (P<0.05). The MTT assay showed that ablation of SMYD3 expression significantly inhibited proliferation of TE13 cells (P<0.05). SMYD3 may participate in the biological activity of esophageal squamous cell carcinoma, as overexpression of SMYD3 correlates with its occurrence and its downregulation inhibits cancer cell proliferation. The shRNA efficiently downregulated SMYD3 in TE13 cells, which represents an SMYD3-interfered cell-test-model for future experiments. RNAi suppression of SMYD3 promoted the expression of RIZ1 in TE13 cells, suggesting a signal transduction pathway between SMYD3 and RIZ1. The SMYD3-RIZ1 pathway may represent a therapeutic target for esophageal squamous cell carcinoma.

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The development and progression of esophageal cancer are related to the inactivation of RIZ1. Virus infection may also be an important factor.