急性白血病临床出现贫血、肝脾肿大、病程绵长等特征，中医认为属气血不足、痰瘀互结之证。泥蚶，一种海洋生物，在祖国医学中的应用已有悠久历史，具有补益气血、散瘀消痰之功效。海生素（HSS）是从泥蚶中提取的抗肿瘤新药，不但可有效促进白血病细胞凋亡，且可诱导白血病细胞长链非编码RNA（lncRNA）表达。表观遗传在白血病发生发展中具有重要作用，许多表观遗传机制涉及的基因表达都受非编码RNA控制。lncRNA的调控作用在表观遗传学变化研究中日益受到关注，lncRNA可调节基因表达及蛋白功能，对白血病等肿瘤的进展起重要作用。课题组前期研究发现一新的长链非编码RNA—即AALT1，其在海生素处理的白血病K562细胞中发生显著变化，阻断AALT1可降低海生素的抗肿瘤作用。因此，本项目拟研究海生素调控AALT1诱导白血病细胞凋亡及凋亡信号通路变化的机制，为海生素的开发及临床应用奠定坚实的理论基础。

The acute leukemia(AL) is clinically characterized by anemia, hepatosplenomegaly and chronic progress. In the view of tranditional Chinese medicine, it is considered as Qi-Xue deficiency and phlegm-blood stasis. Tegillarca granosa, a kind of marine animals , play an effective roles in replenishing the Qi-Xue and removing the phlegm-blood stasis, and may have a potential role in the treatment of AL. Haishengsu (HSS) is a marine anti-tumor drug which extracted from marine organisms Tegillarca granosa. It not only can effectively increase leukemia cells apoptosis, but also induce the expression of long chain of non-coding RNA molecules in leukemia cells.The epigenetic play an important role in the occurrence and development of leukemia. Most epigenetic mechanisms involved in gene expression are controlled by non-coding RNAs.There has raised great attention to study the regulation effect of non-coding RNA (lncRNA) on epigenetic changes. The lncRNA can regulate gene expression and protein function, which plays an important role in the progress of leukemia and other tumors. Our preliminary study found a new lncRNA name as AALT1, which showed significant changes after leukemia K562 cells treated with Haishengsu. Blocking AALT1 can reduce the antitumor effect of Haishengsu. Therefore, the present work was to study the mechanisms of Haishengsu which regulated AALT1 to induce leukemia cells apoptosis and changes in apoptotic signaling pathways. This study will lay a solid theoretical foundation for Haishengsu development and the clinical application.

急性白血病临床出现贫血、肝脾肿大、病程绵长等特征，中医认为属气血不足、痰瘀互结之证。泥蚶，一种海洋生物，在祖国医学中的应用已有悠久历史，具有补益气血、散瘀消痰之功效。海生素（HSS）是从泥蚶中提取的抗肿瘤新药，不但可有效促进白血病细胞凋亡，还可诱导白血病细胞长链非编码RNA（lncRNA）表达。本项目在白血病细胞和动物模型上探索海生素上调的lncRNA AALT1的功能，对其分子机制展开研究。证实AALT1抑制白血病细胞生长，引起细胞凋亡，介导海生素对肿瘤细胞的杀伤作用。发现Akt－β-catenin是海生素－AALT1发挥作用的下游因子。明确AALT1结合Ago2蛋白。说明AALT1是海生素发挥功能的关键因子，为海生素的开发及临床应用奠定理论基础。