环状RNA广泛参与细胞生长、分化和周期调控，但在无功能垂体瘤侵袭生长中的作用尚不清楚。前期研究表明，circ_0005759在侵袭性无功能垂体瘤中表达上调；沉默胞内circ_0005759可明显抑制垂体瘤细胞的侵袭生长，并下调高迁移率族蛋白A2（HMGA2）水平。分析显示，circ_0005759与let-7a具有潜在的结合靶点，而HMGA2是let-7a的靶基因。生物素偶联miRNA捕获实验显示，转染let-7a mimic的细胞碎片中富集circ_0005759表达。据此，申请人拟确证circ_0005759通过竞争性结合let-7a上调HMGA2的表达增强无功能垂体瘤的侵袭生长。我们将通过体内和体外实验，进一步揭示circ_0005759在无功能垂体瘤侵袭生长中的作用和分子机制。研究结果将初步阐述环状RNA在无功能垂体瘤发生发展中的重要作用，为基于环状RNA的诊治研究提供理论基础。

Circular RNA is widely involved in the regulation of cell growth, differentiation, and cell cycle transition. However, its role in proliferation and invasion of nonfunctioning pituitary adenomas (NFPAs) remains unclear. Our previous study showed that circ_0005759 was significantly overexpressed in invasive NFPAs, comparing to normal pituitary tissue and non-invasive NFPAs. Silencing of circ_0005759 with siRNA suppressed the proliferation and invasion of pituitary tumor cells, accompanying with decreased expression of (high mobility group AT-hook2, HMGA2). Bioinformatics analysis showed that circ_0005759 could potentially be a sponge for let-7a, which can target HMGA2. With biotin coupled let-7a mimic, circ_0005759 was observed to be increased in the let-7a captured fraction compared with the negative control. Taken together, we aim to show that circ_0005759 could promote the proliferation and invasion of NFPAs cells by targeting let-7a- HMGA2 signal. The results of this study will initially explore the vital role of circular RNA in the pathogenesis and development of pituitary adenomas, and also, provide theoretical supports for circular RNA based drug development and discovery of diagnostic markers for NFPAs.