Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Daneshgah St, Tabriz, Iran.
Eur J Med Res. 2024 Mar 6;29(1):154. doi: 10.1186/s40001-024-01754-2.
Glioblastoma multiform (GBM) is among the commonly diagnosed brain malignancies with poor prognosis. CD133 has been introduced as an oncogene in various cancers, like GBM. This study aimed to investigate the significance of CD133 in GBM development using in silico and in vitro techniques.
The TCGA-GBM database was analyzed for the correlational and comparative studies. After selecting the U87MG cell line, CD133-siRNA was transfected into U87MG cells and treated with temozolomide. The cell viability, cell cycle, migration, clonogenicity, and apoptosis of groups were investigated using MTT, flow cytometry, wound-healing, colony formation, and annexin V/PI assays. Using qRT-PCR method, the mRNA expression levels of MMP16, SOX2, RAF1, MAP2K1, MAPK3, PIK3CA, AKT3, mTOR, CDK4, and BCL2 were studied.
CD133 silencing improves apoptosis rate, arrests the cell cycle at the sub-G1 phase, suppresses the clonogenicity of U87MG cells, and inhibits the PI3K/Akt and MAPK pathways via downregulating the RAF1, MAP2K1, MAPK3, PIK3CA, AKT3, and mTOR expression. Besides, combining CD133 silencing with temozolomide treatment considerably inhibits the migration of U87MG cells compared to temozolomide monotherapy.
CD133 can regulate the PI3K/Akt and MAPK pathways and modulate the clonogenicity, apoptosis, and cell cycle of GBM. Combining CD133 silencing with temozolomide treatment considerably increases apoptosis, arrests the cell cycle at the sub-G1, and suppresses migration of U87MG cells compared to temozolomide monotherapy.
多形性胶质母细胞瘤（GBM）是最常见的诊断为脑恶性肿瘤之一，预后不良。CD133 已被介绍为各种癌症中的癌基因，如 GBM。本研究旨在使用计算机和体外技术研究 CD133 在 GBM 发展中的意义。
分析 TCGA-GBM 数据库进行相关和比较研究。选择 U87MG 细胞系后，将 CD133-siRNA 转染到 U87MG 细胞中，并给予替莫唑胺治疗。使用 MTT、流式细胞术、划痕愈合、集落形成和 Annexin V/PI 检测评估各组细胞活力、细胞周期、迁移、克隆形成和细胞凋亡。使用 qRT-PCR 方法研究 MMP16、SOX2、RAF1、MAP2K1、MAPK3、PIK3CA、AKT3、mTOR、CDK4 和 BCL2 的 mRNA 表达水平。
CD133 沉默可提高细胞凋亡率，使 U87MG 细胞周期停滞在 sub-G1 期，抑制 U87MG 细胞的克隆形成，并通过下调 RAF1、MAP2K1、MAPK3、PIK3CA、AKT3 和 mTOR 表达抑制 PI3K/Akt 和 MAPK 通路。此外，与替莫唑胺单药治疗相比，CD133 沉默联合替莫唑胺治疗可显著抑制 U87MG 细胞的迁移。
CD133 可调节 PI3K/Akt 和 MAPK 通路，并调节 GBM 的克隆形成、凋亡和细胞周期。与替莫唑胺单药治疗相比，CD133 沉默联合替莫唑胺治疗可显著增加凋亡、使细胞周期停滞在 sub-G1 期，并抑制 U87MG 细胞的迁移。
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