Upregulation of nuclear transporter, Kpnβ1, contributes to accelerated cell proliferation- and cell adhesion-mediated drug resistance (CAM-DR) in diffuse large B-cell lymphoma.
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.
Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
Song
S
He
Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
Xiaobing
X
Miao
Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
Yaxun
Y
Wu
Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
Xinghua
X
Zhu
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China.
Xianjing
X
Miao
Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
Haibing
H
Yin
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China.
Yunhua
Y
He
Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
Chunsun
C
Li
Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
Yushan
Y
Liu
Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
Xiaoyun
X
Lu
Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
Yali
Y
Chen
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China. wangyuchannt@126.com.
Yuchan
Y
Wang
Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China. xuxiaohongnantong@126.com.
Xiaohong
X
Xu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation; D028961:beta Karyopherins / Q000235:genetics* / Q000378:metabolism
C424166:KPNB1 protein, human; D028961:beta Karyopherins
Cell adhesion-mediated drug resistance (CAM-DR); Diffuse large B-cell lymphoma (DLBCL); Kpnβ1; NF-κB p65; Proliferation