长链非编码RNA GAS5调控心肌细胞凋亡及其机制研究

Cardiovascular disease is the leading cause of death worldwide. Cardiomyocyte apoptosis is correlated with the development of cardiovascular disease. Long noncoding RNA (lncRNA) is an important regulator participating in the pathogenesis of cardiovascular disease. However, the molecular mechanism remains to be elucidated. Long noncoding RNA GAS5 (Growth Arrest Specific Transcript 5) has been found to function as tumor suppressor in cancer. However, the role of GAS5 in the pathogenesis of heart disease remains unknown. This project will elucidate the mechanism of GAS5 regulating cardiomyocyte apoptosis and myocardial infarction. We will conduct the following experiment. (1) The role of lncRNA GAS5 regulating cardiomyocyte apoptosis and myocardial infarction. (2) To explore whether GAS5 regulates cardiomyocyte apoptosis and myocardial infarction through miR-23a. (3) To test whether miR-23a regulates apoptosis through MnSOD. This study will reveal the molecular mechanism of GAS5 regulating cardiomyocyte apoptosis and myocardial infarction. The accomplishment of this project will provide novel target for treatment of cardiovascular disease.

心血管疾病是人类健康的威胁，心肌细胞凋亡和心血管疾病紧密相关。Long noncoding RNA (lncRNA)是调节心血管疾病的重要因子，其调节心肌细胞凋亡的分子机制有待研究。lncRNA GAS5（Growth Arrest Specific Transcript 5）在肿瘤中发挥抑癌基因的作用，然而其在心脏疾病过程中的功能尚不清楚。此申请项目拟探究GAS5调节心肌细胞凋亡和心肌梗死的分子机理。研究的主要内容包括：（1）lncRNA GAS5在心肌细胞凋亡以及心肌梗死中的作用；（2）研究lncRNA GAS5是否通过miR-23a调节心肌细胞凋亡以及心肌梗死过程。（3）研究miR-23a是否通过MnSOD调节心肌细胞凋亡。预期目标是阐明lncRNA GAS5在心肌细胞凋亡和心肌梗死中的作用及分子机制。本项研究将为心血管疾病的预防和治疗提供新的靶点，具有重要的理论意义和科学价值。

心肌细胞凋亡和心肌梗死的分子机制是心血管基础医学研究中重要内容，而长链非编码RNA（Long noncoding RNA, LncRNA）是当今生命科学研究的热点和难点，其作用的分子机制复杂，研究证实lncRNA在各种疾病的致病中发挥着重要的作用。本项研究采用体外培养的原代心肌细胞和心肌缺血再灌注损伤的动物模型研究lncRNA分子的功能及其分子机制。研究发现抑制lncRNA GAS5的表达能够减少缺血再灌注损伤所引起的心肌梗死面积，GAS5调节miR-23a的表达，miR-23a通过MnSOD调节心肌细胞凋亡和心肌梗死过程，抑制miR-23a能显著抑制IR所引起心肌细胞凋亡程度。我们深入研究lncRNA在心肌细胞凋亡中的作用机制，发现过表达lncRNA FTX可以显著抑制心肌细胞凋亡程度，过表达miR-29b-1-5p显著减弱lncRNA FTX对心肌细胞凋亡的抑制作用。LncRNA FTX通过miR-29b-1-5p和bcl2l2途径调节心肌细胞凋亡过程。本项研究揭示了lncRNA GAS5等调控心肌细胞凋亡的分子机制，为心血管疾病的预防及治疗提供理论基础和科学依据。