环状RNA（circ-NR3C1）在膀胱癌中结合miRNA及编码蛋白的双重作用与调控机制研究

环状RNA（circRNA）结构稳定、具有组织相关性, 对其功能及作用机制的探讨是基因表达调控研究领域的新内容。目前认为circRNA主要作为内源性miRNA“海绵”发挥作用；新近研究则对circRNA有了新认识：circRNA具有潜在编码功能。我们前期首次鉴定了一种膀胱癌相关circRNA （circ-NR3C1），其在膀胱癌起抑癌作用。初步研究显示：circ-NR3C1具有结合hsa-miR-27a-3p和编码蛋白的双重功能。本研究拟进一步解析circRNA-NR3C1结合hsa-miR-27a-3p对Cyclin D1的表达调控作用及机制，并阐明circRNA-NR3C1编码蛋白结合FOXO1抑制MMP-2转录作用。本项目的成功实施，将从全新的角度阐明circRNA结合miRNA及编码蛋白的双重作用，有望首次揭示人体细胞内源性circRNA编码功能，具有潜在膀胱癌治疗临床应用价值。

Circular RNA (circRNA) is usually stably expressed in a tissue-specific manner. The study on the function and mechanism of circRNA is a new content in the field of gene expression regulation. At present, circRNA is thought to play an important role as an endogenous miRNA sponge. Recent studies have a new understanding of circRNA: circRNA has a potential coding function. We first identified a bladder cancer associated circRNA (circ-NR3C1), which was significantly reduced in bladder cancer, and had an inhibitory effect on growth and invasion of bladder cancer cells. Preliminary studies show that circ-NR3C1 has the dual functions of binding hsa-miR-27a-3p and coding proteins. This study will further reveal the role and underlying mechanism of circRNA-NR3C1/hsa-miR-27a-3p interaction in regulation of Cyclin D1 expression, and clarify the effects of circRNA-NR3C1 encoding protein/FOXO1 complex on inhibition of MMP-2 gene transcription. This work will elucidate both the miRNA sponge and protein encoding roles of the endogenous circRNA, as well as provide a novel strategy for the treatment of bladder cancer.