Zhang Tingting, Ma Guangtao, Zhang Yan, Huo Hongda, Zhao Yuqian
School of Basic Medical Science, Central South University, Changsha, Hunan 410078, P.R. China.
Department of Neurosurgery, Daqing Oil Field General Hospital, Daqing, Heilongjiang 163000, P.R. China.
Oncol Rep. 2017 Sep;38(3):1751-1759. doi: 10.3892/or.2017.5824. Epub 2017 Jul 17.
MicroRNAs (miRNAs) play a vital role in tumour biological and pathologic processes. In the present study, we aimed to detect the expression and biological role of miR-216b in glioma. Our data showed that miR-216b was significantly downregulated in human glioma tissues and cells. Ectopic expression of miR-216b inhibited the proliferation and invasion of U87 and U251 cells and suppressed the growth of xenograft tumours in vivo. Bioinformatic and luciferase reporter analyses identified Forkhead box protein M1 (FoxM1) as a direct target of miR-216b. Overexpression of miR-216b inhibited the expression of FoxM1 in glioma cells. Rescue experiments demonstrated that co-transfection of FoxM1 lacking the 3'-untranslated region partially prevented miR‑216b-induced inhibition of glioma cell growth and invasion. In vivo studies indicated that ectopic expression of miR-216b impeded the proliferation of glioma xenograft tumours in nude mice, coupled with a decreased in FoxM1 protein expression and the percentage of Ki-67-positive tumour cells. Taken together, our results provide evidence of the suppressive activity of miR‑216b in glioma, which is largely ascribed to downregulation of FoxM1. Restoration of miR-216b may provide a novel potential therapeutic agent for glioma.
微小RNA(miRNA)在肿瘤生物学和病理过程中发挥着至关重要的作用。在本研究中,我们旨在检测miR-216b在胶质瘤中的表达及其生物学作用。我们的数据显示,miR-216b在人类胶质瘤组织和细胞中显著下调。miR-216b的异位表达抑制了U87和U251细胞的增殖和侵袭,并抑制了体内异种移植肿瘤的生长。生物信息学和荧光素酶报告基因分析确定叉头框蛋白M1(FoxM1)是miR-216b的直接靶点。miR-216b的过表达抑制了胶质瘤细胞中FoxM1的表达。挽救实验表明,共转染缺失3'非翻译区的FoxM1可部分阻止miR-216b诱导的胶质瘤细胞生长和侵袭抑制。体内研究表明,miR-216b的异位表达阻碍了裸鼠胶质瘤异种移植肿瘤的增殖,同时FoxM1蛋白表达和Ki-67阳性肿瘤细胞百分比降低。综上所述,我们的结果提供了miR-216b在胶质瘤中具有抑制活性的证据,这主要归因于FoxM1的下调。恢复miR-216b可能为胶质瘤提供一种新的潜在治疗药物。