长链非编码RNA-RNCR3调控新生血管生成的分子机制研究

Angiogenesis is a complex process that is regulated by numerous gene regulators. It occurs in situations such as wound and fracture healing, tumor growth, atherosclerosis, and some eye disease. LncRNAs have emerged as novel regulatory components of eukaryotic genome, and key players in numerous physiologic and pathological processes. To date, little was known about the role of lncRNAs in angiogenesis. We will apply the easily observable vascular system of the retina as a model to investigate the role of lncRNAs in angiogenesis. Our previous study has revealed that RNCR3 is differentially expressed during retinal neovascularization (RNV). However, it is still unknown about the potential mechanism of RNCR3-mediated angiogenesis. Herein, we will detect RNCR3 expression pattern in hypoxia-induced RF/6A cell model or oxygen-induced retinopathy mouse model at different time points, clarify the role of RNCR3 in RNV through in vitro or in vivo intervention of RNCR3 expression, and reveal the molecular mechnasim of RNCR3-mediated RNV. This study will provide a novel insight into the mechanism underlying angiogenesis and a novel target to hinder pathological angiogenesis.

新生血管生成是一个受到多种因子调控的复杂过程，常常伴发于创伤修复、肿瘤生长、动脉粥样硬化和部分眼科疾病。长链非编码RNA（lncRNAs）是一类重要的基因元件，可调控许多生理和病理过程。迄今为止，lncRNAs如何调控新生血管生成仍然知之甚少。我们拟采用易于观察的视网膜血管系统作为研究对象，揭示lncRNAs在新生血管生成中的调控作用。我们前期研究发现，在视网膜新生血管生成时，lncRNA-RNCR3的表达发生显著变化，而关于RNCR3调控新生血管生成的机制仍然不清楚。本项目拟建立RF/6A细胞缺氧模型和小鼠视网膜新生血管模型，分析多个压力和时间点下RNCR3的表达规律；基于对RNCR3的表达干预，明确RNCR3在新生血管生成过程的调控作用；基于生物信息学和分子生物学技术，阐明RNCR3调控新生血管生成的分子机制。研究有望揭示新生血管生成的调控新机制，为病理性血管生成的干预提供新靶点。

新生血管生成是一个受到多种因子调控的复杂过程，常常伴发于糖尿病、动脉粥样硬化、肿瘤生长和部分眼科疾病。长链非编码RNA（lncRNAs）是一类重要的基因元件，可调控许多生理和病理过程。我们主要采用易于观察的视网膜血管系统作为研究对象，揭示lncRNAs在新生血管生成中的调控作用。我们发现，在糖尿病和动脉粥样硬化等引起的血管病变中，lncRNA-RNCR3的表达发生显著地上调。动物水平上，RNCR3表达沉默抑制病理性视网膜新生血管的生成和血管渗漏，对成熟的血管系统起到保护作用；细胞水平上，RNCR3参与调控内皮细胞的活性、增殖、凋亡、迁移和成管等功能。机制研究发现，RNCR3、miR-185和KLF2基因构成调控网络参与调节内皮细胞功能。研究从非编码RNA角度揭示了血管新生的调控新机制，为病理性血管生成的干预提供一个新靶点。