Department of Neurosurgery, The Laiyang Central Hospital of Yantai, Yantai, Shandong, 264000, China.
Department of Neurosurgery, The General Hospital of Jinan Military Area Command, Jinan, Shandong, 250000, China.
Cell Biol Int. 2020 May;44(5):1156-1167. doi: 10.1002/cbin.11314. Epub 2020 Feb 24.
Glioma is the most common brain tumor malignancy with high mortality and poor prognosis. Emerging evidence suggests that cancer stem cells are the key culprit in the development of cancer. MicroRNAs have been reported to be dysregulated in many cancers, while the mechanism underlying miR-150-5p in glioma progression and proportion of stem cells is unclear. The expression levels of miR-150-5p and catenin beta 1 (CTNNB1, which encodes β-catenin) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The expression levels of downstream genes of the Wnt/β-catenin pathway and stem cell markers were detected by qRT-PCR. Tumorigenesis was investigated by cell viability, colony formation, and tumor growth in vitro and in vivo. The interaction between miR-150-5p and β-catenin was explored via bioinformatics analysis and luciferase activity assay. We found that miR-150-5p was downregulated in glioma and its overexpression inhibited cell proliferation, colony formation, and tumor growth. Moreover, miR-150-5p directly suppressed CTNNB1 and negatively regulated the abundances of downstream genes of the Wnt/β-catenin pathway and stem cell markers. Furthermore, miR-150-5p expression was decreased and β-catenin level was enhanced in CD133+ glioma stem cells. Knockdown of miR-150-5p contributed to CD133- cells with stem cell-like phenotype, whereas overexpression of miR-150-5p suppressed CD133+ glioma stem cell-like characteristics. In conclusion, miR-150-5p inhibited the progression of glioma by controlling stem cell-like characteristics via regulating the Wnt/β-catenin pathway, providing a novel target for glioma treatment.
神经胶质瘤是最常见的脑肿瘤恶性肿瘤，死亡率和预后差。新出现的证据表明，癌症干细胞是癌症发展的关键罪魁祸首。已经报道了 microRNAs 在许多癌症中失调，而 miR-150-5p 在神经胶质瘤进展和干细胞比例中的作用机制尚不清楚。通过定量实时聚合酶链反应（qRT-PCR）和 Western blot 测量 miR-150-5p 和连环蛋白 β 1（编码 β-连环蛋白）的表达水平。通过 qRT-PCR 检测 Wnt/β-连环蛋白通路和干细胞标志物的下游基因的表达水平。通过细胞活力、集落形成和体内外肿瘤生长来研究肿瘤发生。通过生物信息学分析和荧光素酶活性测定探讨了 miR-150-5p 和 β-连环蛋白之间的相互作用。我们发现 miR-150-5p 在神经胶质瘤中下调，其过表达抑制细胞增殖、集落形成和肿瘤生长。此外，miR-150-5p 直接抑制 CTNNB1 并负调控 Wnt/β-连环蛋白通路和干细胞标志物的下游基因的丰度。此外，CD133+神经胶质瘤干细胞中 miR-150-5p 的表达降低，β-连环蛋白水平升高。miR-150-5p 的敲低有助于 CD133-细胞具有干细胞样表型，而过表达 miR-150-5p 抑制 CD133+神经胶质瘤干细胞样特征。总之，miR-150-5p 通过调节 Wnt/β-连环蛋白通路控制干细胞样特征来抑制神经胶质瘤的进展，为神经胶质瘤的治疗提供了一个新的靶点。
