Abstract：
Lymphoma is the most common malignant tumor arising from immune system. Recently, DNA polymerase epsilon subunit 2 (POLE2) was identified to be a tumor promotor in a variety of malignant tumors. However, the biological role of POLE2 in lymphoma is still largely unclear. In our present study, the expression patterns of POLE2 in lymphoma tissues were identified by immunohistochemistry (IHC) staining of human tissue microarray. Cell viability was determined by CCK-8 assay. Cell apoptosis and cycle distribution were evaluated by Annexin V and PI staining, respectively. Cell migration was analyzed by transwell assay. Tumor growth in vivo was observed by a xenograft model of mice. The potential signaling was explored by human phospho-kinase array and immunoblotting. POLE2 was significantly upregulated in human lymphoma tissues and cells. POLE2 knockdown attenuated the proliferation, migration capabilities of lymphoma cells, as well as induced cell apoptosis and cycle arrest. Moreover, POLE2 depletion impaired the tumor growth in mice. Furthermore, POLE2 knockdown apparently inhibited the activation of β-Catenin and downregulated the expression of Wnt/β-Catenin signaling-related proteins. POLE2 knockdown suppressed the proliferation and migration of lymphoma cells by inhibiting Wnt/β-Catenin signaling pathway. POLE2 may serve as a novel therapeutic target for lymphoma.
摘要：
淋巴瘤是由免疫系统引起的最常见的恶性肿瘤。最近,DNA聚合酶ε亚基2（POLE2）被鉴定为多种恶性肿瘤的肿瘤启动子。然而,POLE2在淋巴瘤中的生物学作用尚不清楚.在我们目前的研究中，通过人组织芯片的免疫组织化学（IHC）染色鉴定了淋巴瘤组织中POLE2的表达模式。通过CCK-8测定确定细胞活力。通过膜联蛋白V和PI染色评估细胞凋亡和周期分布，分别。通过transwell测定法分析细胞迁移。通过小鼠的异种移植模型观察体内肿瘤生长。通过人磷酸激酶阵列和免疫印迹探索了潜在的信号传导。POLE2在人淋巴瘤组织和细胞中显著上调。POLE2敲低减弱增殖，淋巴瘤细胞的迁移能力，以及诱导细胞凋亡和周期阻滞。此外，POLE2消耗损害了小鼠的肿瘤生长。此外，POLE2敲低明显抑制β-Catenin的激活并下调Wnt/β-Catenin信号相关蛋白的表达。POLE2敲低通过抑制Wnt/β-Catenin信号通路抑制淋巴瘤细胞增殖和迁移。POLE2可作为淋巴瘤的新治疗靶点。
