Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Fengtai, Beijing, China.
J Mol Neurosci. 2020 May;70(5):759-768. doi: 10.1007/s12031-020-01486-y. Epub 2020 Feb 6.
Minichromosome maintenance 10 (MCM10) plays an important role in DNA replication and is expressed in a variety of tumors, including glioma. However, its role and mechanism in glioma remain elusive. The purpose of this study was to examine the molecular function of MCM10 in glioblastoma cell lines in vitro and to further investigate the molecular mechanisms in the network mediated by MCM10. Cell proliferation, invasion, and migration were investigated in the absence of MCM10 mediated by RNA interference (RNAi) in U87 and U251 cell lines. Microarray data were obtained from U87 cells infected with a lentivirus expressing a small interfering RNA (siRNA) targeting MCM10, and ingenuity pathway analysis (IPA) was performed. Molecular signaling pathways, gene functions, and upstream and downstream regulatory genes and networks were analyzed. MCM10 was positively stained in human glioblastoma multiforme (GBM) samples according to immunohistochemistry. Silencing MCM10 in U87 and U251 cells significantly reduced cell proliferation, migration, and invasion. In U87 cells transfected with MCM10, 274 genes were significantly upregulated, while 313 genes were downregulated. IPA revealed that MCM10 is involved in the IGF-1 signaling pathway, and calcitriol appears to be a significant upstream regulator of MCM10. Other factors, such as TWIST1 and Stat3, also interact within the MCM10-mediated network. Our data indicate that MCM10 is involved in the regulation of GBM in vitro and may provide more evidence for understanding the molecular mechanisms of this fatal disease.
微小染色体维持蛋白 10（MCM10）在 DNA 复制中发挥着重要作用，并且在多种肿瘤中表达，包括神经胶质瘤。然而，其在神经胶质瘤中的作用和机制仍不清楚。本研究旨在体外研究 MCM10 在神经胶质瘤细胞系中的分子功能，并进一步研究 MCM10 介导的网络中的分子机制。通过 RNA 干扰（RNAi）在 U87 和 U251 细胞系中缺失 MCM10 来研究细胞增殖、侵袭和迁移。从感染靶向 MCM10 的小干扰 RNA（siRNA）慢病毒的 U87 细胞中获得微阵列数据，并进行 ingenuity 通路分析（IPA）。分析分子信号通路、基因功能以及上游和下游调节基因和网络。根据免疫组织化学，MCM10 在人类多形性胶质母细胞瘤（GBM）样本中呈阳性染色。沉默 U87 和 U251 细胞中的 MCM10 显著降低了细胞增殖、迁移和侵袭。在转染 MCM10 的 U87 细胞中，274 个基因显著上调，而 313 个基因下调。IPA 显示 MCM10 参与 IGF-1 信号通路，而钙三醇似乎是 MCM10 的重要上游调节剂。其他因素，如 TWIST1 和 Stat3，也在 MCM10 介导的网络中相互作用。我们的数据表明，MCM10 参与了体外 GBM 的调节，并且可能为了解这种致命疾病的分子机制提供更多证据。
