Department of Neurosurgery, Affiliated Hospital of Taishan Medical University, Taian, 271000, Shandong, People's Republic of China.
Life Science Research Centre of Taishan Medical University, Taian, 271000, Shandong, People's Republic of China.
J Neurooncol. 2018 Oct;140(1):15-26. doi: 10.1007/s11060-018-2927-0. Epub 2018 Jun 18.
Runt-related transcription factor 3 (RUNX3) exerts a tumor suppressor gene associated with gastric and other cancers, including glioma. However, how its anti-tumor mechanism in functions glioma is unclear.
We assayed expression of RUNX3 with a tissue microarray (TMA), frozen cancer tissues and malignant glioma cell lines using immunohistochemistry, qRT-PCR and Western bolt analysis. Cell proliferation, invasion, cell cycle distribution and apoptosis were also examined to confirm the effect of RUNX3 medicated malignant phenotype. TOP/FOP experiment was used to detect the β-catenin/Tcf-4 transcription activity by RUNX3.
Enforced RUNX3 expression inhibited proliferation and invasion, induced cell cycle arrest and promoted apoptosis in vitro and in vivo, Bim siRNA partically reversed the effect of RUNX3-induced apoptosis in LN229 and U87 cells, suggesting a dependent role of Bim-caspase pathway. Moreover, Mechanism investigations revealed that restoration of RUNX3 suppressed β-catenin/Tcf-4 transcription activity.
RUNX3 plays a pivotal role in glioma initiation and progression as a tumor suppressor via attenuation of Wnt signaling, highlighting it as a potential therapeutic target for glioma.
Runt 相关转录因子 3（RUNX3）作为一种与胃癌和其他癌症（包括神经胶质瘤）相关的肿瘤抑制基因发挥作用。然而，其在神经胶质瘤中的抗肿瘤机制尚不清楚。
我们使用组织微阵列（TMA）、冷冻的癌症组织和恶性神经胶质瘤细胞系，通过免疫组织化学、qRT-PCR 和 Western blot 分析来检测 RUNX3 的表达。还检测了细胞增殖、侵袭、细胞周期分布和细胞凋亡，以证实 RUNX3 介导的恶性表型的作用。通过 RUNX3 进行 TOP/FOP 实验，检测 β-连环蛋白/Tcf-4 转录活性。
强制表达 RUNX3 可抑制体外和体内的增殖和侵袭，诱导细胞周期停滞并促进细胞凋亡，Bim siRNA 部分逆转了 RUNX3 诱导 LN229 和 U87 细胞凋亡的作用，表明 Bim-caspase 途径的依赖性。此外，机制研究表明，RUNX3 的恢复抑制了β-连环蛋白/Tcf-4 转录活性。
RUNX3 作为一种肿瘤抑制因子，通过抑制 Wnt 信号通路，在神经胶质瘤的发生和进展中发挥着关键作用，强调其作为神经胶质瘤潜在治疗靶点的潜力。
