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Upregulation of nuclear transporter, Kpnβ1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma

  • Original Article – Cancer Research
  • Published:
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Abstract

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 β1 (Kpnβ1) is a member of the Karyopherin β superfamily of nuclear transport proteins. In addition to the nuclear import function, Kpnβ1 is associated with the occurrence of tumors. This study investigated the expression and biologic function of Kpnβ1 in diffuse large B-cell lymphoma (DLBCL).

Methods

The prognostic value of Kpnβ1 expression was evaluated using immunohistochemical staining. The role of Kpnβ1 on cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) was also determined.

Results

We demonstrated that Kpnβ1 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 Kpnβ1 was correlated with Ki-67 (P < 0.001). Kaplan–Meier curve showed that high expression of Kpnβ1 was significantly associated with shorter overall survival. In addition, Kpnβ1 was associated with the proliferation of DLBCL cells. Importantly, we found that Kpnβ1 could interact with p65 and promote CAM-DR via accelerating NF-κB activation in DLBCL.

Conclusions

Patients with tumors highly expressing Kpnβ1 have poorer overall survivals. Kpnβ1 interacts with p65 and enhances CAM-DR.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81201858, 81372537) and Natural Scientific Foundation of Jiangsu Province Grant (No. BK2012231).

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    Authors and Affiliations

    1. Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China

      Song He, Xiaobing Miao, Yaxun Wu, Xinghua Zhu, Haibing Yin, Chunsun Li, Yushan Liu, Xiaoyun Lu & Yali Chen

    2. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China

      Xianjing Miao, Yunhua He & Yuchan Wang

    3. Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China

      Xiaohong Xu

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    1. Song He
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    Correspondence to Yuchan Wang or Xiaohong Xu.

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    Song He and Xiaobing Miao have contributed equally to this work.

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    He, S., Miao, X., Wu, Y. et al. Upregulation of nuclear transporter, Kpnβ1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma. J Cancer Res Clin Oncol 142, 561–572 (2016). https://doi.org/10.1007/s00432-015-2057-4

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