急性髓系白血病(AML)是成人最常见的白血病，预后差。p53失活是AML的关键驱动因素。我们的研究显示长链非编码RNA (lncRNA)与p53活性密切相关 (Leukemia, 2017)，但机制尚需探索。前期工作发现AML中lncRNA MALAT1的表达显著增加,并与p53含量呈明显负相关，且其能促进肿瘤生长。AML中p53很少突变，MDM2对其活性发挥了重要的负向调控作用。我们发现MALAT1能与p53蛋白结合，并能增加p53与MDM2之间的结合；MALAT1还可促进MDM2的表达，同时还能激活AML另一关键调控分子mTOR。我们推测MALAT1一方面通过与p53结合促进MDM2与p53的结合；一方面通过mTOR促进MDM2的表达，从而使p53表达下降、促进肿瘤生长。该推测还将通过细胞学实验、模式动物和临床样本进一步论证。如果本课题得以成功，将可能为提高AML疗效提供新靶点。

Acute myeloid leukemia (AML) is the most common form of leukemia in adults and has a poor prognosis. It is established that inactivation of p53 is a key driver of AML. Our recent work has demonstrated that long noncoding RNA (lncRNA) is closely related to the activity of p53 (Leukemia, 2017), but the underlying mechanisms are waiting to be explored. Our preliminary data showed that the expression of lncRNA MALAT1 that was inversely related to p53 content was significantly increased, and it could promote tumor growth in AML. It is known that p53 mutation rarely occurs in AML. MDM2 exerts an important role in inversely regulating on the p53 activity. Furthermore, we found that MALAT1 bound to p53 protein and it promoted the binding between p53 and MDM2; MALAT1 also promoted MDM2 expression while mTOR, another key regulator of AML, was activated. Therefore, we speculate that MALAT1 promotes the binding of MDM2 to p53 by its own capacity of p53 binding; meanwhile, MALAT1 promotes MDM2 expression through mTOR activation, resulting in a decrease of p53 expression to promote tumor growth. Clearly, this hypothesis needs to be demonstrated by further analysis in cell models, animals in vivo and clinical samples. If the project is successful, it is very probable to provide a new target for therapeutic improvement of AML treatment.