PER2 inhibits proliferation and stemness of glioma stem cells via the Wnt/β-catenin signaling pathway
PER2 inhibits proliferation and stemness of glioma stem cells via the Wnt/β-catenin signaling pathway
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PER2 通过 Wnt/β-catenin 信号通路抑制胶质瘤干细胞的增殖和干性
DOI：
10.3892/or.2020.7624
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发表时间：
2020-08-01
期刊：
影响因子：
4.2
通讯作者：
Niu, Zhanfeng
中科院分区：
文献类型：
--
作者：
Ma, Dede;Hou, Li;Niu, Zhanfeng
胶质母细胞瘤是一种高度恶性的肿瘤，其含有称为胶质瘤干细胞（GSC）的干细胞样细胞，其与胶质瘤发生、复发和预后不良的风险增加相关。生物钟基因，周期生物钟2（PER 2）的表达已被发现在各种类型的癌症中被抑制。然而，PER 2在GSC中的确切作用和潜在机制仍不清楚。本研究表明，与非干细胞胶质瘤细胞相比，PER 2 mRNA和蛋白在胶质瘤干细胞中表达下调，提示PER 2可能参与了胶质瘤的恶性过程。此外，功能研究表明，PER 2过表达可诱导GSC停滞在G 0/G1期，并抑制其增殖，干细胞和侵袭能力在体外和体内。随后，Wnt/β-连环蛋白信号传导途径被鉴定为GSC中PER 2的靶标。这些结果表明，PER 2在调节GSC的干性中起关键作用，并提供了克服GSC影响的新的治疗靶点。
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/beta -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.