核糖体蛋白(RP)L23除参与蛋白质生物合成外，还调节细胞增殖、发育、凋亡等过程。迄今对RPL23在MDS发病中的作用及机制还知之甚少。我们的前期研究显示RPL23高表达的MDS造血细胞凋亡抵抗、白血病转化率高，其机制有待进一步探讨。C-Myc具有抑制细胞凋亡作用，Miz1是c-Myc关联锌指蛋白，抑制c-Myc转录活性。研究显示RPL23负性调控Miz1活性。为此，我们提出假说：RPL23可能通过负性调节Miz1，激活c-Myc，抑制MDS细胞凋亡。为了验证这一假说，我们将通过人MDS细胞系MDS-L和正常人CD34(＋)细胞；采用慢病毒载体转染、基因导入、RNA干扰、免疫沉淀、WB等手段，探讨RPL23在MDS细胞凋亡异常中作用，明确RPL23通过Miz1/c-Myc分子途径对MDS细胞凋亡的调控机制。本研究将从RPL23这个新视点揭示MDS凋亡抵抗发生机制，为MDS治疗提供新的思路。

Ribosomal proteins (RP) L23 carries out a range of extraribosomal functions, such as regulating cellular proliferation, differentiation and apoptosis, besides being involved in the progress of protein biosynthesis. The role of RPL23 in the pathogenesis of myelodysplastic syndromes (MDS) still remains unknown. Our previous studies have showed that MDS patients with RPL23 over-expressed presented apoptosis-resistance of hematopoietic cells in bone marrow, higher tranformation to acute myeloid leukemia and shorter survival time. The mechanism underling the phenomenon is still not well understood. C-Myc has been proved to play an important role in the process of cellular apoptosis. Miz1, Myc-associated zinc-finger protein can inhibit the transcription activity of c-Myc. A recent study reported that RPL23 is a negative regulator of Miz1-dependent transactivation. Our hypothesis is that RPL23 may have an essential function in restricting Miz1-dependent apoptosis and controling the ability of Myc to inhibit cell apoptosis. To prove the hypothesis, methods such as transfection with lentivirus, RNA interferon, in vitro colony formation cultivation, flow cytometry, real time PCR, immunoprecipitation and western blot will be used on MDS cell line(MDS-L) and normal CD34(+) hematopoietic stem cells to identify the role of Miz1/c-Myc pathway in the apoptosis-resistance of MDS cells mediated by RPL23. This study will provide a new insight into the pathopysiology of MDS and a clue to search for new therpy for MDS.