Study On P53-Mediated Regulatory Mechanism Of Ran Transcription In Multiple Myeloma Cells

Introduction:Multiple myeloma (MM) is a malignant hematopoietic disease originated from plasma cells, leading to related organ or tissue damage (ROTI). It is suggested that 15000 new cases reported each year in western countries with median survival time of 4-5 years. With the development of novel agents against myeloma in the last decade, the prognosis of myeloma patients has been promoted remarkably while disease re-occurrence remains notable. It is still difficult to manage relapsed/refractory myeloma which is an incurable disease.Objective:Previous study had detected abnormality of ran transcription in relapsed myeloma cells with P53 mutation compared with the status at diagnosis. We assumed that there probably an association between these genes. Here, in this study, we investigate the role of P53 on ran transcription in myeloma cells.Methods and Results:Using real-time fluorescence quantitative PCR, H-929 and MM1.S cells in the 8 human myeloma cell lines have highest transcriptional activity of Ran (P< 0.05). Ran transcription decreased in MM1.S after treated with Nutlin-3a compared with vehicle (P < 0.05). Meanwhile, using western blot, P53 protein expression in MM1.S cells increased while Ran protein expression decreased in a manner of time dependence. With detection by P53 luciferase reporter assay, ran transcription decreased with involvement of plasmid increased to 25ng compared with vehicle which is not in a manner of dose dependence.Conclusion:In this study, we demonstrated that ran is a target gene of P53 regulation in myeloma cells for the first time. In addition, it is also the first time to reveal that ran gene plays an important role in myeloma cells. It provides new evidence and promising aspect on the road towards curing relapsed/refractory multiple myeloma.