MiR-1299 promotes the synthesis and secretion of prolactin by inhibiting FOXO1 expression in drug-resistant prolactinomas
MiR-1299 promotes the synthesis and secretion of prolactin by inhibiting FOXO1 expression in drug-resistant prolactinomas
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MiR-1299通过抑制耐药催乳素瘤中FOXO1的表达促进催乳素的合成和分泌
DOI：
10.1016/j.bbrc.2019.09.070
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发表时间：
2019-11-26
影响因子：
3.1
通讯作者：
Zhu, Yonghong
中科院分区：
文献类型：
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作者：
Xiao, Zheng;Wang, Zongming;Zhu, Yonghong
催乳素瘤是临床上常见的颅内肿瘤。当血清催乳素水平没有得到控制，尽管管理的多巴胺受体激动剂，条件被称为抗药性催乳素瘤。耐药催乳素瘤催乳素持续分泌的机制尚不清楚。microRNA在肿瘤的发生、发展以及化疗耐药性中起着重要作用。本研究旨在探讨miRNA在催乳素耐药瘤中调节催乳素分泌的机制。我们首先发现miR-1299在耐药泌乳素瘤中升高，并通过miRNA测序和荧光素酶测定以靶向方式抑制FOXO 1。然后，我们证实，FOXO 1结合到催乳素基因的启动子，抑制其表达，通过染色质免疫沉淀定量PCR和细胞学实验。最后，原发肿瘤细胞中miR-1299的抑制或过表达证实，耐药泌乳素瘤通过促进miR-1299表达和减少细胞内FOXO 1来促进泌乳素分泌。这些结果表明FOXO 1和miR-1299是耐药泌乳素瘤以及其他垂体疾病的潜在治疗靶点。(C)2019爱思唯尔公司All rights reserved.
Prolactinoma is a clinically common intracranial tumor. When serum prolactin levels are not controlled despite administration of a dopamine agonist, the condition is referred to as drug-resistant prolactinoma. The mechanism underlying persistent prolactin secretion in drug-resistant prolactinoma remains unclear. MicroRNAs play an important role in tumorigenesis and development as well as chemotherapeutic resistance. This study was conducted to investigate the mechanism by which miRNA regulates prolactin secretion in drug-resistant prolactinoma. We first found that miR-1299 was elevated in drug-resistant prolactinoma and inhibited FOXO1 in a targeted manner through miRNA sequencing and luciferase assays. We then confirmed that FOXO1 binds to the promoter of the prolactin gene to inhibit its expression through chromatin immunoprecipitation-quantitative PCR and cytological experiments. Finally, inhibition or overexpression of miR-1299 in primary tumor cells confirmed that drug-resistant prolactinoma promoted prolactin secretion by promoting miR-1299 expression and reducing intracellular FOXO1. These results indicate that FOXO1 and miR-1299 are potential therapeutic targets for drug-resistant prolactinoma as well as other pituitary diseases. (C) 2019 Elsevier Inc. All rights reserved.