横纹肌肉瘤(RMS)细胞过度增殖，调控细胞分化的信号通路活性受抑制，被认为是治疗失败导致肿瘤复发的根源。研究表明转录因子MyoD在调控RMS细胞分化过程中起关键作用，但其活性明显受抑制，分子机制不明。MEF2是调控MyoD活性的重要转录因子，前期我们证明骨骼肌细胞内MEF2C乙酰化修饰可以增强MyoD转录活性，对诱导细胞分化至关重要,而体内外预试验显示：RMS细胞内MEF2C处于去乙酰化状态，导致其转录活性下降，调控能力减弱。本研究以RD细胞为研究对象，采用细胞内mRNA干扰合成、报告基因检测及DNA结合功能检测等手段研究：RD细胞内MEF2C乙酰化状态对MyoD活性及RD细胞增殖的影响；同时探讨乙酰化酶P300及去乙酰化酶HDAC4/5对RD细胞内MEF2C乙酰化的影响，为临床上探索横纹肌肉瘤的分子靶向治疗提供理论依据。

Resistance of rhabdomyosarcoma to current therapies remains one of the key issues in the treatment. Signaling pathways that mediate cell differentiation defects in cell-arrest programs in RMS cells may result in resistance. In our initial study on the differentiation defect in RMSs , we demonstrated that MyoD was present as a key role in regulating muscle cell differentiation , but was a poor transcriptional activator in vivo. In this present study, we examined the molecular mechanisms that prevent MyoD activity in RMSs, focusing on the RD cell line derived from an RMS. We demonstrate effects of MEF2 acetylation on MyoD activity with methods such as: reporter assay ;Electrophoretic mobility shift assays (EMSA);RNAi and so on. further examined the relationship between MEF2C acetylation and P300 or HDAC4/5. Therefore, the identification of the molecular mechanisms in rhabdomyosarcoma presents a critical step for the rational development of molecular targeted drugs.