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The long noncoding RNA-H19/miRNA-93a/ATG7 axis regulates the sensitivity of pituitary adenomas to dopamine agonists
Zerui Wu1, Yongzhi Zheng1, Wanqun Xie1
1Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Abstract:
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.
Insights
Long noncoding RNA H19 enhances dopamine agonist treatment for prolactinomas. This study reveals the H19-miR-93-ATG7 pathway, offering a new therapeutic target for pituitary tumors.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Dopamine agonists (DAs) are first-line treatment for prolactinomas.
- Long noncoding RNA H19 (H19) is downregulated in pituitary adenomas and linked to tumor progression.
- The role of H19 in DA treatment for prolactinomas remains unclear.
Purpose of the Study:
- To investigate the synergistic effect of H19 and DA treatment in prolactinomas.
- To elucidate the underlying molecular mechanism of H19 in DA treatment.
- To identify H19 as a potential therapeutic target for prolactinomas.
Main Methods:
- In vitro and in vivo experiments on prolactinoma cells.
- Analysis of H19, miR-93a, and ATG7 expression.
- Luciferase reporter assays to confirm binding sites.
Main Results:
- H19 demonstrated a synergistic effect with DA treatment in prolactinomas.
- H19 promotes ATG7 expression by inhibiting miR-93a.
- miR-93a directly targets and regulates ATG7 mRNA expression.
- Low miR-93 expression correlates with DA resistance.
Conclusions:
- The H19-miR-93-ATG7 axis plays a crucial role in DA treatment of prolactinomas.
- This pathway represents a potential therapeutic strategy for human prolactinomas.
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