lncRNA-B230352I09在小鼠心脏再生中的功能与机制研究

LncRNA-B230352I09 is a functionally unknown RNA that is highly differentially expressed in the neonatal rat cardiac tissue. Our previous study found that lncRNA-B230352I09 promoted cardiomyocyte proliferation and correlated with cardiac regeneration. According to the bioinformatics analysis of gene co-expression network, Igfbp3 may be the regulatory target of lncRNA-B230352I09, which regulates cardiac regeneration through affecting Wnt signaling pathways. Based on these date, we will analyze the temporal and spatial expression patterns of lncRNA-B230352I09 before and after birth, myocardial damage in mice. Furthermore, we observe the effect of lncRNA-B230352I09 overexpression or silencing on proliferation and hypoxia tolerance of primary cardiomyocytes, and preliminarily explore the effects and possible mechanisms of lncRNA-B230352I09 on cardiac regeneration. In addition, we establish a model of myocardial injury by apical excision to investigate the role of lncRNA-B230352I09 in cardiac regeneration and regard the Wnt-Igfbp3 Signaling pathway as the cutting point to demonstrate the specific mechanism of lncRNA-B230352I09 to promote cardiac regeneration. So far, there is no report on the function of LncRNA-B230352I09 and its relationship with cardiac regeneration, thus this study is of originality and will elucidate the role of LncRNA-B230352I09 in cardiac regeneration. It will provide new clues for understanding the specific molecular mechanism of cardiac regeneration.

LncRNA-B230352I09是差异高表达于新生乳鼠心脏组织中、功能未知的lncRNA。前期发现：lncRNA-B230352I09能促进心肌细胞增殖、与心脏再生相关；根据基因共表达网络等生物信息学分析提示Igfbp3可能为B230352I09调控靶标，通过影响Wnt信号通路参与调控心脏再生。本研究拟分析①B230352I09在小鼠出生前后、心肌损伤前后的时空表达规律；②通过过表达或沉默B230352I09分析其对原代心肌细胞增殖及缺氧耐受的影响；③通过心尖切除术模型，探讨B230352I09在心脏再生过程的作用，同时以Wnt-Igfbp3信号通路为切入点，论证其促进心脏再生的具体机制。目前有关lncRNA-B230352I09的功能及与心脏再生的关系，国内外均未见报道，本课题研究具有源头创新性，将有助于阐明其在心脏再生中的作用，为人们理解心脏再生的具体分子机制提供新的线索。

LncRNA B230352I09是我们采用lncRNA 测序技术筛选到的、一条差异高表达于新生一天小鼠心脏组织中、功能未知的lncRNA。前期发现：lncRNA B230352I09促进心肌细胞增殖，通过生物信息学分析发现其可能通过靶向 Igfbp3发挥作用。通过本课题的研究，我们发现：lncRNA B230352I09在心脏中主要表达于心肌细胞，定位于细胞核，lncRNA B230352I09明显促进心肌细胞增殖，抑制缺氧后心肌细胞凋亡，改善缺氧后心肌细胞线粒体功能，通过靶向IGFBP3调控心肌细胞的增殖和缺氧耐受。综上，通过本课题的研究，我们阐明了lncRNA B230352I09心肌保护作用及可能机制，将有助于促进对心脏再生分子机制的理解，并可能为心肌梗死的治疗提供潜在的干预靶标。