机构:[1]Beijing Neurosurgical Institute, Capital Medical University, Beijing, China, 100050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, Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui, China, 230001[3]Department of Neurosurgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, China, 266003[4]Beijing Neurosurgical Institute, Capital Medical University, Beijing, China, 100050,Key Laboratory of Central Nervous System Injury Research, Center of Brain Tumor of Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China, 100050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
Prolactinomas are the most frequently observed pituitary adenomas. Prolactinomas invasion is a key risk factor associated with operation results, and it is highly correlated with clinical prognosis. Nuclear receptor subfamily 2 group C member 2 (NR2C2) first cloned from testis is involved in the invasion and metastasis of several human tumors. In 46 patients with prolactinamas, the expression levels of CCNB1, Notch2, and NR2C2 was determined with tissue micro-array (TMA). The association between NR2C2 levels and clinical parameters was established with univariate analysis. The levels of Notch2 and CCNB1 were analyzed by RT-PCR and western blot techniques. The average methylation levels of the NR2C2 promoter were 0.505 and 0.825 in invasive prolactinomas (IPA) and non-IPA groups, respectively (p = 0.013). Univariate analysis also showed that there is a significant relationship between high NR2C2 expression and invasion (x(2) = 7.043, p = 0.008), prolactin granules (x(2) = 8.712, p = 0.003), and tumor size (x(2) = 4.261, p = 0.039). With the knockdown of NR2C2, cell proliferation was inhibited. Genes related to epithelial-mesenchymal transition (EMT) induced the apoptosis in MMQ cells. In addition, the level of Notch2 and CCNB1 were down-regulated with the knockdown of NR2C2. Moreover, miR-129-5p reduced mRNA levels of NR2C2, and they inhibited cell proliferation by inducing apoptosis levels of MMQ cells. Our findings proved NR2C2 played the important role in tumorigenesis tumor invasion of prolactinomas; moreover, NR2C2 is identified as a potential target.
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, 100050
通讯作者:
通讯机构:[*1]Beijing Neurosurgical Institute, Capital Medical University, Beijing, China, 100050,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 Zhuang,Liu Qian,Wang Fei,et al.The role of NR2C2 in the prolactinomas[J].OPEN CHEMISTRY.2018,16(1):817-826.doi:10.1515/chem-2018-0080.
APA:
Wang Zhuang,Liu Qian,Wang Fei,Lan Xiaolei,Guo Jing...&Zhang Yazhuo.(2018).The role of NR2C2 in the prolactinomas.OPEN CHEMISTRY,16,(1)
MLA:
Wang Zhuang,et al."The role of NR2C2 in the prolactinomas".OPEN CHEMISTRY 16..1(2018):817-826