Incubation Base of National Key Laboratory for Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.
Institute of Human Stem Cells, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.
Oncol Rep. 2020 Aug;44(2):533-542. doi: 10.3892/or.2020.7624. Epub 2020 May 27.
Glioblastoma is a highly malignant tumor that contains stem‑like cells known as glioma stem cells (GSCs), which lare associated with an increased risk of glioma occurrence, recurrence and poor prognosis. Circadian clock gene, period circadian clock 2 (PER2) expression has been revealed to be inhibited in various types of cancer. However, the precise role and potential mechanisms of PER2 in GSCs remains unclear. The present study demonstrated that PER2 mRNA and protein expression was downregulated in GSCs compared with non‑stem glioma cells, which indicated that PER2 could be involved in the malignant process of glioma. Furthermore, functional studies revealed that PER2 overexpression could induce GSC arrest at the G0/G1 phase and suppress their proliferation, stemness and invasion ability in vitro and in vivo. Subsequently, the Wnt/β‑catenin signaling pathway was identified as the target of PER2 in GSCs. These results indicated that PER2 plays a critical role in regulating the stemness of GSCs and provides a novel therapeutic target to overcome the effects of GSCs.
胶质母细胞瘤是一种高度恶性的肿瘤,其中包含被称为神经胶质瘤干细胞(GSCs)的干细胞样细胞,这些细胞与胶质瘤发生、复发和预后不良的风险增加有关。昼夜节律基因周期蛋白 PER2 的表达已被证实存在于多种类型的癌症中受到抑制。然而,PER2 在 GSCs 中的精确作用和潜在机制尚不清楚。本研究表明,与非干细胞性神经胶质瘤细胞相比,GSCs 中 PER2 mRNA 和蛋白表达下调,这表明 PER2 可能参与了胶质瘤的恶性过程。此外,功能研究表明,PER2 过表达可诱导 GSC 在 G0/G1 期停滞,并抑制其在体外和体内的增殖、干性和侵袭能力。随后,鉴定出 Wnt/β-catenin 信号通路是 PER2 在 GSCs 中的靶标。这些结果表明,PER2 在调节 GSCs 的干性中发挥着关键作用,并为克服 GSCs 的影响提供了一个新的治疗靶点。