The long noncoding RNA-H19/miRNA-93a/ATG7 axis regulates the sensitivity of pituitary adenomas to dopamine agonists
The long noncoding RNA-H19/miRNA-93a/ATG7 axis regulates the sensitivity of pituitary adenomas to dopamine agonists
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长非编码RNA-H19/miRNA-93a/ATG7轴调节垂体腺瘤对多巴胺激动剂的敏感性
DOI：
10.1016/j.mce.2020.111033
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Zhe Bao Wu
中科院分区：
文献类型：
--
作者：
Zerui Wu;Yong Zhi Zheng;Wan Qun Xie;Qun li;Yong Zhang;Bo Han Ren;Lin Cai;Yijun Cheng;Hao Tang;Zhipeng Su;Zhe Bao Wu
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。我们以前的研究表明，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。在本研究中，我们报道了H19与DA治疗催乳素瘤在体外和体内的协同作用。H19通过抑制miR-93 a表达促进垂体瘤细胞中ATG 7的表达。此外，miR-93和H19之间的潜在结合位点被证实，并且先前在DA耐药泌乳素瘤中发现了miR-93的低表达。此外，我们发现miR-93 a通过靶向ATG 7 mRNA来调节ATG 7表达。总之，我们的研究已经确定了H19-miR-93-ATG 7轴在泌乳素瘤DA治疗中的作用，这可能是人类泌乳素瘤的潜在治疗靶点。
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 andin 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.
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