新型长链非编码RNA在心脏再生中的功能研究

成人心肌再生能力非常低，缺血引起坏死的心肌细胞很难再生，继而被纤维瘢痕组织代替，并最终导致心力衰竭。因此研究心脏再生修复对心脏疾病的治疗具有重要意义。我们之前的研究证明非编码RNA家族中微小RNA，miR-17-92可以促进心肌增殖并保护心梗环境下的心脏功能。而家族成员中占80%的长链非编码RNA(LncRNA)对心脏再生与疾病调控目前未见报道。因此我们在本项目前期工作中通过基因芯片、生物信息学和时空表达谱等筛选出调控心肌再生修复的新型LncRNA, Lnc-HeartPRO。在此基础上将通过功能获得性与缺失性研究, 在整体动物、细胞和分子水平全面研究Lnc-HeartPRO对心脏再生修复与疾病的调控作用。并深入研究Lnc-HeartPRO 在表观遗传学层面影响心脏再生修复的分子机制。该项目将鉴定出可以促进心脏再生修复，保护心脏功能的新型LncRNA，为缺血性心脏病患者提供全新的治疗策略。

Ischemic heart disease resulting in myocardial infarction and heart failure is the leading cause of morbidity and mortality. Cardiomyocytes in adult hearts are terminally differentiated cells that have exited from the cell cycle. Death of mature cardiomyocytes in pathological cardiac conditions (e.g. heart attack) and the lack of sufficient regenerative capacity of adult hearts are primary causes of heart failure and mortality. Therefore, regeneration of cardiomyocytes and prevention of heart remodeling is the key for treatment of heart diseases. We previously reported that miR-17-92 cluster is required and sufficient for cardiomyocytes proliferation and preserved cardiac function after myocardial infarction. In this project, we focus on long non-coding RNA (LncRNA), which is 80% of the transcription of non-coding RNA. By using LncRNA microarray approach, we have screened regeneration-related LncRNAs in heart tissue from myocardial infarction, and further narrowed down the LncRNA candidates with important criteria. The preliminary data showed that Lnc-HeartPRO is a very promising LncRNA for heart regeneration. Therefore, we will use both gain- and loss-of-function approaches to elucidate the function of Lnc-HeartPRO in heart regeneration in vivo and in vitro. Furthermore, we will test the hypothesis that Lnc-HeartPRO promotes the cardiac regeneration through epigenetic way in which Lnc-HeartPRO recruit PRC2 members to regulate the cardiac regeneration-related gene expression. We believe that the project will first identified novel LncRNAs, promoting cardiac regeneration and protect heart function under cardiac diseases. That provides new insight for cardiac regeneration and new therapeutic treatment for heart diseases.