垂体催乳素细胞腺瘤（PRLoma）在标准化治疗之后复发，其肿瘤细胞表观遗传学改变是关键因素。项目组前期通过高通量芯片筛选出环状RNA分子circNT5E在PRLoma组织中异常高表达，干扰其表达可降低大鼠垂体腺瘤细胞的侵袭性和对溴隐亭的抵抗性。结合竞争性内源性RNA调控机制，我们推测：PRLoma中异常增高的circNT5E介导肿瘤复发。本研究拟以circNT5E为切入点体内外观察其对PRLoma细胞侵袭性及对溴隐亭抵抗的影响；探讨circNT5E通过竞争性内源性RNA机制调控miR-422a，从而靶向激活NT5E/CD73、PI3K/Akt信号通路介导PRLoma细胞获得高侵袭性及溴隐亭抵抗能力；研究上游蛋白因子hnRNPA2B劫持circNT5E进入外泌体传递肿瘤细胞侵袭表型，从而阐明PRLoma复发的可能机制。研究结果可望为提高PRLoma综合治疗的疗效提供实验依据。

The epigenetic changes of Pituitary prolactinoma (PRLoma) tumor cells is the key mechanism of PRLoma recurrence after the standard treatment. It was found that circRNA-NT5E(circNT5E) was upregulated in PRLoma tumor tissues, which was screened by high-throughput microarray. Knockdown of circNT5E reduced the invasion of PRLoma cells and bromocriptine resistance. Combined with the competitive endogenous RNA(ceRNA) regulatory mechanism, we hypothesized that the abnormally high expressed circNT5E mediates PRLoma recurrence. The aim of this study was to investigate the effect of circNT5E on the invasion and bromocriptine resistance of PRLoma cells in vivo and in vitro. And, we want to deeply explore the ceRNA regulatory mechanism of circNT5E in PRLoma, which regulates miR-422a, and thus activates NT5E/CD73 and PI3K/Akt signaling pathways, which mediates the invasion and bromocriptine resistance of PRLoma. In addition, we will study hnRNPA2B hijack circNT5E into exosomes to transmit tumor cell invasion phenotype. These results will be expected to provide a new experimental basis for improving the efficacy of PRLoma comprehensive therapy.