NRD1, which encodes nardilysin protein, promotes esophageal cancer cell invasion through induction of MMP2 and MMP3 expression.
Bottom Line: Furthermore, nardilysin expression was significantly associated with poorer prognosis (P = 0.0258).The invasiveness of NRD1-knockdown TE1 and TE5 esophageal cancer cell lines was less than that of the negative control siRNA-transfected cell lines.Expression of MMP2 and MMP3 mRNA was significantly lower in NRD1-knockdown TE5 cells than in negative control siRNA-transfected cells.
Affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.Show MeSH
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Mentions: We showed that high levels of NRD1 mRNA expression were correlated with T classification, N classification and tumor stage in ESCC tissues. Furthermore, nardilysin protein expression was correlated with patients’ prognosis. Therefore, we studied the biological significance of NRD1 using esophageal cancer cell lines. Western blot analysis showed that all six esophageal cancer cell lines expressed nardilysin at various levels (Fig.3a). NRD1 mRNA expression and nardilysin protein expression were well correlated. The highest nardilysin expression was detected in TE1 cells, and the other five remaining cell lines had moderate or low nardilysin expression. Next, we examined the transition of nardilysin expression by Western blot analysis of protein extracts of TE1 and TE5 cell lines transfected with NRD1 specific siRNAs because the highest nardilysin expression was detected in TE1 cells, and moderate nardilysin expression was detected in TE5 cells. Three different siRNAs (siRNA1, 2, and 3) were transfected into TE1 and TE5 (Fig.3b). The expression of nardilysin protein in TE1 was most suppressed by treatment with siRNA1. Similar results were observed in TE5 cells. Thus, to knockdown the endogenous NRD1, we used siRNA1 in the following experiments.
Affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.