机构：[1]Beijing Neurosurgical Institute, Capital Medical University, Beijing, China研究所北京市神经外科研究所首都医科大学附属天坛医院[2]Department of Neurosurgery, Xinjiang Uygur Autonomous Region People’s Hospital, Xinjiang, China[3]Department of Neurosurgery, Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui Province, China[4]Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China
Prolactinomas are the most frequently observed pituitary adenomas (PAs), and 5%-18% tumors were resistant to the dopamine agonists (DAs). MicroRNAs (miRNAs) dysfunction play a key role in tumorigenesis. Agilent miRNA and an expression chip were used for six prolactinomas and three normal pituitary specimens. Differentially expressed genes were confirmed by RT-qPCR. The level of DDR1 and SAT1 was determined with tissue micro-array (TMA) and western blot. A MMQ cell line was used for functional experiments. We have identified 5-miRNA and 12 target gene signatures of prolactinomas through gene ontology analysis. miRNA-199a-5p was selected for experiments that integrated the results from prolactinomas specimens and a rat prolactinoma model induced by 17-b-estradiol. Tumors with low miRNA-199a-5p had a significantly invasive behavior and a higher tumor volume (p<0.05). DDR1 and SAT1, target genes of miRNA-199a-5p, had higher H-scores in the invasive group than those of the non-invasive group through TMA. An overexpression of miRNA-119a-5p suppressed the PRL secretion and the cell viability through upregulated the apoptosis level in MMQ cells (p<0.01). Furthermore, we found the target genes expression of DDR1 and SAT1 were affected by miRNA-199a-5p regardless of mRNA levels or protein levels. This study provided evidence that downregulation of miRNA-199a-5p may contribute to prolactinoma tumorigenesis.
基金：
Beijing Natural Science Foundation of ChinaBeijing Natural Science Foundation [7162035]; Beijing High-level Talent Plan [2015-3-040]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81502141]; National High Technology Research and Development Program of China (863 Program)National High Technology Research and Development Program of China [2015AA020504]
第一作者机构：[1]Beijing Neurosurgical Institute, Capital Medical University, Beijing, China[2]Department of Neurosurgery, Xinjiang Uygur Autonomous Region People’s Hospital, Xinjiang, China
通讯作者：
通讯机构：[*1]Beijing Neurosurgical Institute, Capital Medical University, Beijing, China[*2]Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714)：
Wang Jichao,Guo Jing,Wang Fei,et al.miRNA-199a-5p functions as a tumor suppressor in prolactinomas[J].OPEN CHEMISTRY.2019,17(1):506-515.doi:10.1515/chem-2019-0036.
APA：
Wang Jichao,Guo Jing,Wang Fei,Cao Lei,Liu Qian...&Zhang Yazhuo.(2019).miRNA-199a-5p functions as a tumor suppressor in prolactinomas.OPEN CHEMISTRY,17,(1)
MLA：
Wang Jichao,et al."miRNA-199a-5p functions as a tumor suppressor in prolactinomas".OPEN CHEMISTRY 17..1(2019):506-515
