Dopamine agonists (DAs), such as cabergoline and bromocriptine, are the first-line clinical treatment for prolactinomas. Our previous study demonstrated that long noncoding RNA H19 expression is frequently downregulated in human primary pituitary adenomas and is negatively correlated with tumor progression. However, the significance and mechanism of H19 in the DA treatment of prolactinomas are still unknown. In this study, we reported that H19 had a synergistic effect with DA treatment on prolactinomas in vitro and in vivo. Mechanistically, H19 promoted ATG7 expression in pituitary tumor cells by inhibiting miR-93a expression. In addition, a potential binding site between miR-93 and H19 was confirmed, and low expression of miR-93 was previously found in DA-resistant prolactinomas. Furthermore, we showed that miR-93a regulates ATG7 expression by targeting ATG7 mRNA. In conclusion, our study has identified the role of the H19-miR-93-ATG7 axis in DA treatment of prolactinomas, which may be a potential therapeutic target for human prolactinomas.

多巴胺激动剂（DA），如卡麦角林和溴隐亭，是泌乳素瘤的一线临床治疗药物。我们之前的研究表明，长链非编码RNA H19的表达在人原发性垂体腺瘤中经常下调，并且与肿瘤进展呈负相关。然而，H19在DA治疗泌乳素瘤中的意义和机制仍不清楚。在这项研究中，我们报道了 H19 与 DA 治疗在体外和体内对泌乳素瘤具有协同作用。从机制上来说，H19通过抑制miR-93a的表达来促进垂体肿瘤细胞中ATG7的表达。此外，还证实了 miR-93 和 H19 之间的潜在结合位点，并且之前在 DA 抗性催乳素瘤中发现了 miR-93 的低表达。此外，我们发现 miR-93a 通过靶向 ATG7 mRNA 来调节 ATG7 表达。总之，我们的研究确定了 H19-miR-93-ATG7 轴在 DA 治疗泌乳素瘤中的作用，这可能是人类泌乳素瘤的潜在治疗靶点。