Department of Hematology, Zibo Central Hospital, Zibo, 255000, Shandong, China.
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Mol Cell Biochem. 2024 Mar;479(3):487-497. doi: 10.1007/s11010-023-04738-8. Epub 2023 Apr 25.
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.
淋巴瘤是最常见的起源于免疫系统的恶性肿瘤。最近，DNA 聚合酶 ε 亚基 2（POLE2）被鉴定为多种恶性肿瘤中的肿瘤促进因子。然而，POLE2 在淋巴瘤中的生物学作用在很大程度上仍不清楚。在本研究中，通过免疫组织化学（IHC）染色人类组织微阵列鉴定了 POLE2 在淋巴瘤组织中的表达模式。通过 CCK-8 测定法测定细胞活力。通过 Annexin V 和 PI 染色分别评估细胞凋亡和细胞周期分布。通过 Transwell 测定分析细胞迁移。通过小鼠异种移植模型观察体内肿瘤生长。通过人类磷酸激酶阵列和免疫印迹法探索潜在的信号通路。POLE2 在人类淋巴瘤组织和细胞中显著上调。POLE2 敲低减弱了淋巴瘤细胞的增殖、迁移能力，并诱导细胞凋亡和周期停滞。此外，POLE2 耗竭损害了小鼠中的肿瘤生长。此外，POLE2 敲低明显抑制了 β-连环蛋白的激活，并下调了 Wnt/β-连环蛋白信号通路相关蛋白的表达。POLE2 通过抑制 Wnt/β-连环蛋白信号通路抑制淋巴瘤细胞的增殖和迁移。POLE2 可能成为淋巴瘤的一种新的治疗靶点。
