Upregulation of nuclear transporter, Kpnβ1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma
Upregulation of nuclear transporter, Kpnβ1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma
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核转运蛋白 Kpnbeta1 的上调有助于弥漫性大 B 细胞淋巴瘤中加速细胞增殖和细胞粘附介导的耐药性 (CAM-DR)。
DOI：
10.1007/s00432-015-2057-4
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发表时间：
2016-03-01
影响因子：
3.6
通讯作者：
Xu, Xiaohong
中科院分区：
文献类型：
--
作者：
He, Song;Miao, Xiaobing;Xu, Xiaohong
背景核仁蛋白参与了货物蛋白和某些RNA的穿梭，穿过核孔复合体进出细胞核。核仁组成蛋白β1(KPNβ1)是核转运蛋白超家族中的一员。除了核进口功能外，KPNβ1还与肿瘤的发生有关。本研究探讨KPNβ1在弥漫性大B细胞淋巴瘤(DLBCL)中的表达及其生物学功能。结果DLBCL B细胞和DLBCL细胞株中KPNβ1的mRNA和蛋白表达水平均显著高于正常CD19纯化B细胞。免疫组织化学分析显示KPNβ1的表达与Ki-67呈正相关(P<；0.001)。Kaplan-Meier曲线显示KPNβ1高表达与总生存期缩短显著相关。此外，KPNβ1与DLBCL细胞的增殖有关。重要的是，我们发现KPNβ1可通过促进DLBCL中的NF-kappa B活化而与p65相互作用，促进CAM-DR的表达。结论高表达KPNβ1的肿瘤患者总体生存率较低。KPNβ1与p65相互作用，增强CAM-DR。
Background The Karyopherin proteins are involved in the shuttling of cargo proteins, and certain RNAs, across the nuclear pore complex into and out of the cell nucleus. Karyopherin beta 1 (Kpn beta 1) is a member of the Karyopherin beta superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpn beta 1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpn beta 1 in diffuse large B-cell lymphoma (DLBCL).Methods The prognostic value of Kpn beta 1 expression was evaluated using immunohistochemical staining. The role of Kpn beta 1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined.Results We demonstrated that Kpn beta 1 mRNA and protein expression levels were significantly higher in DLBCL B-cells and DLBCL cell lines than in normal CD19 purified B-cells. Immunohistochemical analysis suggested that the expression of Kpn beta 1 was correlated with Ki-67 (P < 0.001). Kaplan-Meier curve showed that high expression of Kpn beta 1 was significantly associated with shorter overall survival. In addition, Kpn beta 1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpn beta 1 could interact with p65 and promote CAM-DR via accelerating NF-kappa B activation in DLBCL.Conclusions Patients with tumors highly expressing Kpn beta 1 have poorer overall survivals. Kpn beta 1 interacts with p65 and enhances CAM-DR.