Shen Da-Wei, Li Yun-Long, Hou Yu-Jie, Xu Zhi-Dan, Li Yong-Zhe, Chang Jian-Yong
a Department of Neurosurgery , Yidu Central Hospital of Weifang , Weifang , P. R. China.
b Department of Hand and Foot Surgery , Yidu Central Hospital of Weifang , Weifang , P. R. China.
Biosci Biotechnol Biochem. 2019 Jun;83(6):1035-1044. doi: 10.1080/09168451.2019.1591260. Epub 2019 Apr 11.
Pituitary adenomas (PA) are commonly occurring benign neoplasms. Identification of molecular pathway resulting in pituitary tumorigenesis remains challenges in endocrine oncology. The present study was conducted with aim of investigating the role of microRNA-543 (miR-543) in PA development. Up-regulated miR-543 and downregulated Smad7 were observed in PA tissues. Afterwards, the specific mechanism of miR-543 and Smad7 in PA were determined with the use of ectopic expression, depletion and reporter assay experiments. Smad7 was confirmed as a target gene of miR-543. HP75 cells treated with overexpressed miR-543 exhibited increased cell proliferation, migration and invasion, while decreased cell apoptosis as well as expression of Cleaved caspase-3 and Cleaved caspase-8 were observed. Suppression of miR-543 contributed to an opposite trend to the above findings. Based on the findings, the inhibition of miR-543 was found to play a tumor suppressive role in PA through the down-regulation of Wnt/β-catenin pathway by negatively regulating Smad7.
垂体腺瘤(PA)是常见的良性肿瘤。确定导致垂体肿瘤发生的分子途径仍然是内分泌肿瘤学中的挑战。本研究旨在探讨微小RNA - 543(miR - 543)在PA发生发展中的作用。在PA组织中观察到miR - 543上调和Smad7下调。随后,通过异位表达、敲低和报告基因检测实验确定了miR - 543和Smad7在PA中的具体机制。Smad7被确认为miR - 543的靶基因。用过表达的miR - 543处理的HP75细胞表现出细胞增殖、迁移和侵袭增加,同时观察到细胞凋亡减少以及Cleaved caspase - 3和Cleaved caspase - 8的表达降低。抑制miR - 543导致与上述结果相反的趋势。基于这些发现,发现抑制miR - 543通过负调控Smad7下调Wnt/β - 连环蛋白通路,从而在PA中发挥肿瘤抑制作用。