苹果酸酶代谢在基因表达调控中的作用机制研究

Metabolism enzymes and small molecule metabolites in gene regulation represented an undiscovered and newly epigenetic regulation. We previously found that malic enzymes played an important role in cancer progression. However, less is known about malic enzymes in cell fate. Here, we observed an inhibition of adipocyte differentiation and NADPH levels in malic enzymes down-regulated 3T3-L1 cells. Based on above results, we will first confirm whether malic enzymes are involved in adipocyte differentiation. Then we will explore if malic enzymes-NADPH pathway in gene expression is depended on epigenetics. This study aims to investigate the role of malic enzymes in cell fate and cell differentiation. It may drive metabolism-gene regulation research and provide novel therapeutic targets.

代谢酶和代谢小分子对基因表达的调控是一种新的尚未被深入挖掘的表观遗传调控方式，正越来越受到人们的关注。我们实验室前期的研究发现苹果酸酶途径在肿瘤增殖中扮演重要角色，但对其在细胞中的功能还知之甚少。我们初步的研究结果发现在脂肪前体细胞3T3-L1中敲低苹果酸酶的表达量可以抑制脂肪细胞的分化，同时伴随小分子NADPH的降低。基于上述研究基础，我们拟以脂质代谢为模型，1）阐明苹果酸酶代谢途径的改变是否影响脂肪细胞的分化，以及对细胞命运的影响；2）解析苹果酸酶途径-NADPH是否是通过表观遗传学修饰方式调节了脂肪细胞分化相关基因的表达。本研究旨在研究清楚苹果酸酶代谢途径是否在细胞分化及细胞命运中扮演重要角色，并推动代谢-基因表达调控领域的研究，为临床治疗癌症提供新的思路和有效治疗靶点。