微小RNA-876-3p靶向驱动蛋白家族成员20A以阻断胶质瘤中的JAK2/STAT3信号通路。
MiR-876-3p targets KIF20A to block JAK2/STAT3 pathway in glioma.
作者信息
Tang Jiao, Xu Jie, Zhi Zhongwen, Wang Xiang, Wang Yu, Zhou Yong, Chen Rui
机构信息
Department of Neurology, Yan Cheng City No. 1 People's Hospital Yancheng City, Jiangsu Province, China.
Department of General Surgery, Huai'an First People's Hospital and The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University Huai'an, Jiangsu Province, China.
出版信息
Am J Transl Res. 2019 Aug 15;11(8):4957-4966. eCollection 2019.
Abstract
Aberrant expression of miRNAs has been reported to be involved in the development and progression of glioma. But the function of miR-876-3p in glioma is unknown. We found that miR-876-3p is significantly downregulated in glioma tissues and cell lines. Overexpression of miR-876-3p suppressed glioma cell proliferation, epithelial-mesenchymal transition, migration, and invasion. By prediction combining with luciferase reporter assay, we identified that miR-876-3p could decrease the expression of KIF20A by directly targeting the region of its 3'UTR. Furthermore, we observed that overexpression of miR-876-3p inhibited the expression of KIF20A, thus blocking the protein kinase JAK2/STAT3 pathway. Overexpressed KIF20A reversed miR-876-3p-induced suppression of glioma cell proliferation, migration, and invasion. We also demonstrated the inhibitory effect of miR-876-3p on tumor growth in glioma using an in vivo model. The miR-876-3p/KIF20A-axis mediated JAK2/STAT3 pathway have therapeutic potential in glioma treatment.
摘要
据报道，微小RNA（miRNA）的异常表达与胶质瘤的发生和发展有关。但miR-876-3p在胶质瘤中的功能尚不清楚。我们发现miR-876-3p在胶质瘤组织和细胞系中显著下调。miR-876-3p的过表达抑制了胶质瘤细胞的增殖、上皮-间质转化、迁移和侵袭。通过预测结合荧光素酶报告基因检测，我们确定miR-876-3p可通过直接靶向KIF20A的3'非翻译区来降低其表达。此外，我们观察到miR-876-3p的过表达抑制了KIF20A的表达，从而阻断了蛋白激酶JAK2/STAT3通路。过表达的KIF20A逆转了miR-876-3p诱导的对胶质瘤细胞增殖、迁移和侵袭的抑制作用。我们还使用体内模型证明了miR-876-3p对胶质瘤肿瘤生长的抑制作用。miR-876-3p/KIF20A轴介导的JAK2/STAT3通路在胶质瘤治疗中具有治疗潜力。
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