Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
Department of Neurosurgery, Yeungnam University College of Medicine, Yeungnam University Hospital, Daegu, Republic of Korea.
Sci Rep. 2020 Oct 26;10(1):18238. doi: 10.1038/s41598-020-75457-z.
Mucin 1 (MUC1) is a transmembrane glycoprotein involved in tumorigenesis of diverse cancers. However, the role of MUC1 in glioblastoma (GBM) has not yet been fully explored. In this study, the anticancer mechanism of MUC1 suppression in GBM was investigated. The expression level of MUC1 was analyzed in human glioma and paired normal brain tissues. MUC1 was overexpressed in GBM and was negatively associated with overall survival. Moreover, we silenced MUC1 to investigate its effect in GBM cell lines and found that knockdown of MUC1 inhibited cell proliferation and resulted in cell cycle arrest at G1 phase. MUC1 silencing decreased the phosphorylation of RB1 and increased the expression of CDKN1B. Gene set enrichment analysis showed that a series of genes related to cell cycle, telomere maintenance and transforming growth factor Beta (TGF-β) signaling in epithelial mesenchymal transition (EMT) were influenced by MUC1 knockdown. Notably, the reduced TERT expression levels combined with impaired telomerase activity and the switching of telomere maintenance mechanism to alternative lengthening of telomeres (ALT) were observed after MUC1 knockdown. Our results support the role of MUC1 in oncological process in GBM which can be developed as a therapeutic target for cell cycle control and telomere maintenance mechanism.
黏蛋白 1（MUC1）是一种参与多种癌症发生的跨膜糖蛋白。然而，MUC1 在胶质母细胞瘤（GBM）中的作用尚未被充分探索。在这项研究中，研究了抑制 MUC1 在 GBM 中的抗癌机制。分析了人胶质瘤和配对正常脑组织中 MUC1 的表达水平。MUC1 在 GBM 中过表达，与总生存期呈负相关。此外，我们沉默 MUC1 以研究其在 GBM 细胞系中的作用，发现敲低 MUC1 抑制细胞增殖，并导致细胞周期停滞在 G1 期。MUC1 沉默降低了 RB1 的磷酸化水平，增加了 CDKN1B 的表达。基因集富集分析表明，一系列与细胞周期、端粒维持和转化生长因子β（TGF-β）信号转导相关的基因在上皮间质转化（EMT）中受到 MUC1 敲低的影响。值得注意的是，在 MUC1 敲低后，观察到 TERT 表达水平降低，端粒酶活性受损，端粒维持机制向端粒替代性延长（ALT）转换。我们的研究结果支持 MUC1 在 GBM 中的肿瘤发生过程中的作用，这可以作为细胞周期控制和端粒维持机制的治疗靶点。
