Export and stabilization of AU-rich element containng mRNA in oral cancer cells

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AU-rich element (ARE) exists in the mRNA transcribed from growth-related genes such as oncogene and cytokine. ARE-containning mRNA (ARE-mRNA) has been shown to be exported and stabilized in the cells transformed with virus oncoprotein. HuR is an RNA-binding protein which has ARE-mRNA are exported to the cytoplasm in oral cancer cells in a CRM1-independent manner and that the knockdown of HuR resulted in changing the characters of oral cancer cells.Immunohistochemical and biochemical analysis revealed that, in oral cancer cells such as HSC3 and Ca922, HuR existed in the cytoplasm and the nucleus whereas almost all HuR was located in the nucleus in normal cells. ARE-mRNAs were also exported and stabilized in oral cancer cells. The export of HuR and ARE-mRNA was not affected by Leptomycin B, which is the inhibitor of CRM1 dependent export pathway, in HSC3 cells. We developed a knockdown system, which is effective for oral cancer cells, using RNAi technique. In HuR-knockdown cells, the export of ARE-mRNA was inhibited. Additionally, those cells failed to make colonies in soft-agar.These findings suggest that HuR and ARE-mRNA are exported to the cytoplasm in oral carcinoma cells by purturbing the normal export pathway and that HuR knockdown has potential as a new therapeutic approach for oral cancer.