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. 2016 Nov 8;7(45):72767-72776.
doi: 10.18632/oncotarget.11889.

Aberrant expression of KPNA2 is associated with a poor prognosis and contributes to OCT4 nuclear transportation in bladder cancer

Jingcheng Zhou  1 , Daoquan Dong  1 , Ran Cheng  1 , Yan Wang  1 , Shuqi Jiang  2 , Yuhong Zhu  1 , Longlong Fan  1 , Xiangming Mao  1 , Yaoting Gui  2 , Zesong Li  3 , Xianxin Li  1   2   4 , Bentao Shi  1
Affiliations

Aberrant expression of KPNA2 is associated with a poor prognosis and contributes to OCT4 nuclear transportation in bladder cancer

Jingcheng Zhou et al. Oncotarget. .

Abstract

Recent studies show that Karyopherin alpha 2 (KPNA2) is up-regulated in quite a number of cancers and associated with poor prognosis. Here, we found that expression levels of KPNA2 and OCT4 are up-regulated in bladder cancer tissues and significantly associated with primary tumor stage and bladder cancer patients' poorer prognosis. Our data also showed decreased cell proliferation and migration rates of bladder cancer cell lines when the expression of KPNA2 and OCT4 was silenced. Meanwhile, cell apoptosis rate was increased. Furthermore, Co-IP and immunofluorescence assay showed the KPNA2 interacts with OCT4 and inhibits OCT4 nuclear transportation when KPNA2 was silenced. Thus, we confirmed that up-regulated KPNA2 and OCT4 expression is a common feature of bladder cancer that is correlated with increased aggressive tumor behavior. Also, we propose that KPNA2 regulates the process of OCT4 nuclear transportation in bladder cancer.

Keywords: KPNA2; OCT4; bladder cancer; nucleo-cytoplasmic transport; prognostic.

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Conflict of interest statement

CONFLICTS OF INTEREST

None.

Figures

Figure 1
Figure 1. KPNA2 and OCT4 are up-regulated in bladder cancer tissues and its association with prognosis
(A–D) Representative IHC staining for KPNA2 and OCT4 expression in bladder cancer tissues and normal bladder tissues. (E, F) The cumulative survival rate was higher in the low protein expression group compared with high KPNA2 or OCT4 expression group.
Figure 2
Figure 2. The mRNA and protein expression level of KPNA2 and OCT4 in bladder cancer cell lines and their changes after transfection with respective siRNAs
(A) Relative KPNA2 and OCT4 mRNA levels were up-regulated in bladder cancer cell lines compared with human uroepithelial cell line. (B) KPNA2 and OCT4 presented higher protein expression in four bladder cancer cell lines. (C, D) Western Blot results indicated KPNA2 and OCT4 specific siRNAs significantly down-regulate the protein expression levels.
Figure 3
Figure 3. Silencing KPNA2 or OCT4 can inhibit cell proliferation
CCK-8 assay was performed to determine cell proliferation rate. (A, B) KPNA2 and OCT4 siRNA inhibit T24 and J82 cell proliferation. EdU assay was used to confirm the proliferation cells. (C, D) Cell proliferation was suppressed after transfection with KPNA2 and OCT4 siRNA in T24 and J82 cells. (E) EdU positive ratio was quantified to Hoechst 33342 positive cells.
Figure 4
Figure 4. Silencing KPNA2 and OCT4 stimulate cell apoptosis and suppress cell migration ability of the bladder cancer cells
Flow cytometry was analyzed to detect early apoptosis rate after transfection with KPNA2 and OCT4 siRNAs compared to negative control. (A–C) Knockdown the expression of KPNA2 and OCT4, apoptotic cells were increased compared with negative control group in T24 and J82 cell lines. (D) Caspase-3 activity was enhanced in the si-KPNA2 and si-OCT4 groups. (E, F) Transwell assay showed that migration of T24 and J82 cells were inhibited after transfected with KPNA2 and OCT4 siRNAs.
Figure 5
Figure 5. Knockdown of KPNA2 inhibits the nuclear translocation of OCT4 in vitro
(A) After knockdown of KPNA2, OCT4 expression was dramatically decreased in the nuclear fraction of the T24 cell line. (B) Co-IP assay was used to examine the association between KPNA2 and OCT4 in vitro. (C–D) The OCT4 fluorescence signal was significantly decreased in cell nucleus as the KPNA2 was silenced in T24 and J82 cell lines.
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