Zhou Fengqi, Cao Wenping, Xu Ran, Zhang Junxia, Yu Tianfu, Xu Xiupeng, Zhi Tongle, Yin Jianxing, Cao Shengwu, Liu Ning, Wang Yingyi, Zhao Chunsheng
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University Nanjing 210029, Jiangsu Province, China.
Am J Transl Res. 2019 Jul 15;11(7):4584-4601. eCollection 2019.
Glioma is one of the most prevalent primary malignant brain tumours among adults, and accumulating evidence has shown that dysregulation of microRNAs (miRNAs) is associated with various types of cancers, including glioma. It is necessary to gain a better understanding of the roles and mechanisms of action of miRNAs in WNT-driven glioblastoma multiforme (GBM). Here, we report that miR-206 inhibits the WNT/β-catenin pathway by directly targeting Frizzled 7 () mRNA and functions as a tumour suppressor in glioma. The expression of miR-206 in human glioma samples and glioma cells was assessed by reverse-transcription quantitative PCR, fluorescence hybridisation, and histological analysis. Cell Counting Kit-8, colony formation, 5-ethynyl-2'-deoxyuridine incorporation, flow-cytometric, wound healing, Transwell invasion, and three-dimensional migration assays were performed to examine glioma cell proliferation, migration, and invasion . The effects of miR-206 were investigated in a xenograft nude-mouse model. MiR-206 expression was significantly lower in glioma specimens than in normal control samples. was confirmed as a direct target gene of miR-206. GBM cell proliferation, migration, and invasion were blocked after restoration of miR-206 expression. Moreover, intracranial glioma models revealed an inhibitory effect of miR-206 on intracranial glioma tumour growth. Our results suggest that miR-206 plays a key role in the blockade of the WNT/β-catenin signalling pathway by down-regulating FZD7 and may be a promising therapeutic agent against malignant glioma and other WNT-driven tumours.
胶质瘤是成人中最常见的原发性恶性脑肿瘤之一，越来越多的证据表明，微小RNA（miRNA）失调与包括胶质瘤在内的多种癌症相关。有必要更好地了解miRNA在WNT驱动的多形性胶质母细胞瘤（GBM）中的作用和作用机制。在此，我们报告miR-206通过直接靶向卷曲蛋白7（FZD7）mRNA抑制WNT/β-连环蛋白信号通路，并在胶质瘤中作为肿瘤抑制因子发挥作用。通过逆转录定量PCR、荧光原位杂交和组织学分析评估miR-206在人胶质瘤样本和胶质瘤细胞中的表达。进行细胞计数试剂盒-8、集落形成、5-乙炔基-2'-脱氧尿苷掺入、流式细胞术、伤口愈合、Transwell侵袭和三维迁移试验，以检测胶质瘤细胞的增殖、迁移和侵袭。在异种移植裸鼠模型中研究了miR-206的作用。胶质瘤标本中miR-206表达明显低于正常对照样本。FZD7被证实为miR-206的直接靶基因。恢复miR-206表达后，GBM细胞的增殖、迁移和侵袭受到抑制。此外，颅内胶质瘤模型显示miR-206对颅内胶质瘤肿瘤生长有抑制作用。我们的结果表明，miR-206通过下调FZD7在阻断WNT/β-连环蛋白信号通路中起关键作用，可能是治疗恶性胶质瘤和其他WNT驱动肿瘤的有前景的治疗剂。
