4.5 Article

The long noncoding RNA-H19/miRNA-93a/ATG7 axis regulates the sensitivity of pituitary adenomas to dopamine agonists

期刊

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2020.111033

关键词

lncRNA H19; Prolactinoma; Dopamine agonist; miRNA-93; ATG7

资金

  1. National Natural Science Foundation of China [81671371, 81801367]
  2. Science and Technology Project of Wenzhou City of China [Y20190144]
  3. Medical Health Science and Technology Research Project of Zhejiang Province of China [2020RC079]
  4. Shanghai Science and Technology Commission [18XD1403400]
  5. Program of Shanghai Academic Research Leader
  6. Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant [20161407]

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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.

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