Department of Pediatric, Huaihe Hospital of Henan University, Kaifeng, Henan, China.
Department of Pediatric, Huaihe Hospital of Henan University, Kaifeng, Henan, China.
Biomed Pharmacother. 2018 Nov;107:689-695. doi: 10.1016/j.biopha.2018.07.171. Epub 2018 Aug 18.
CXC chemokine ligand 9, a member of "cytokine milieu", makes up the microenvironment of lymphoma and plays an important role in the occurrence and development of lymphoma. However, the role of CXC chemokine ligand 9 and its underlying mechanism remains largely unknown in the progression of diffuse large B-cell lymphoma. Wnt/ β -catenin signaling is reported to play an important role in diffuse large B-cell lymphoma, and the overexpression and nuclear accentuation of β-catenin in diffuse large B-cell lymphoma patients' tissues were closely associated with the advanced clinical staging. The present study aimed to explore the effects of CXC chemokine ligand 9 on the progression of diffuse large B-cell lymphoma and determine if β -catenin is involved in this process. We firstly detected the expression pattern of CXC chemokine ligand 9 in diffuse large B-cell lymphoma tissues and cell lines, and determined the relationship between CXC chemokine ligand 9 expression level and patients' progression and prognosis. Then we used the loss/gain of function approach to determine the effects of CXC chemokine ligand 9 on cell viability, apoptosis and migration. Finally, we assessed the expression and subcellular location of β-catenin after CXC chemokine ligand 9 up/down-regulation by Western Blot. Our results showed that CXC chemokine ligand 9 was highly expressed in diffuse large B-cell lymphoma tissues and cell lines, which showed close association with patients' advanced clinical progression and shorter overall survival. Up-regulation of CXC chemokine ligand 9 promoted the viability and migration and repressed the apoptosis of OCI-Ly8 cells, as well as increased β-catenin expression and translocated it from cytoplasm to nuclear, while these effects were abolished when knockdown β-catenin. In conclusion, this work reveals that CXC chemokine ligand 9 promotes the progression of diffuse large B-cell lymphoma in a β-catenin-dependent manner. Our study provides evidence for the mechanism by which CXC chemokine ligand 9 may function as an oncogene and the potential of serving CXC chemokine ligand 9 as a therapeutic target for diffuse large B-cell lymphoma.
CXC 趋化因子配体 9 是“细胞因子环境”的成员，构成了淋巴瘤的微环境，在淋巴瘤的发生和发展中发挥重要作用。然而，CXC 趋化因子配体 9 的作用及其潜在机制在弥漫性大 B 细胞淋巴瘤的进展中仍知之甚少。Wnt/β-catenin 信号通路在弥漫性大 B 细胞淋巴瘤中发挥重要作用，弥漫性大 B 细胞淋巴瘤患者组织中β-catenin 的过度表达和核强调与晚期临床分期密切相关。本研究旨在探讨 CXC 趋化因子配体 9 对弥漫性大 B 细胞淋巴瘤进展的影响，并确定β-catenin 是否参与这一过程。我们首先检测了 CXC 趋化因子配体 9 在弥漫性大 B 细胞淋巴瘤组织和细胞系中的表达模式，并确定了 CXC 趋化因子配体 9 的表达水平与患者进展和预后的关系。然后，我们采用失/功能获得方法来确定 CXC 趋化因子配体 9 对细胞活力、凋亡和迁移的影响。最后，我们通过 Western Blot 检测了 CXC 趋化因子配体 9 上调/下调后β-catenin 的表达和亚细胞定位。结果表明，CXC 趋化因子配体 9 在弥漫性大 B 细胞淋巴瘤组织和细胞系中高表达，与患者晚期临床进展和总生存期缩短密切相关。上调 CXC 趋化因子配体 9 促进了 OCI-Ly8 细胞的活力和迁移，抑制了细胞凋亡，并增加了β-catenin 的表达，使其从细胞质转移到细胞核，而当敲低β-catenin 时，这些作用被消除。综上所述，本研究揭示了 CXC 趋化因子配体 9 以β-catenin 依赖的方式促进弥漫性大 B 细胞淋巴瘤的进展。本研究为 CXC 趋化因子配体 9 作为致癌基因的作用机制以及将 CXC 趋化因子配体 9 作为弥漫性大 B 细胞淋巴瘤治疗靶点提供了证据。
