Expression of KPNB1 in bladder cancer and its role in proliferation and migration of bladder cancer cells

doi:10.3877/cma.j.issn.1674-0785.2024.11.011

Abstract

Abstract:

Objective

To investigate the expression and role of Karyopherin β1 (KPNB1) in bladder cancer based on bioinformatics analysis and cell studies.

Methods

KPNB1 mRNA and protein levels in normal prostate tissues and prostate cancer tissues were obtained from the Cancer Genome Atlas(TCGA), Gene Expression Omnibus (GEO), and the Human Protein Atlas (THPA) databases. The correlation between KPNB1 expression and clinicopathological features of bladder cancer patients, and the expression of KPNB1 in different subgroups of bladder cancer tissues were analyzed. The diagnostic and prognostic value of KPNB1 in bladder cancer was evaluated. Combined with GOKEEG signal pathway enrichment analysis, the mechanism of KPNB1 in bladder cancer was preliminarily explored. Cellular studies were performed using T24 cells with KPNB1 knockdown or overexpression.

Results

Statistical analysis based on the TGGA, GEO, and THPA databases showed that, compared with normal bladder tissues, KPNB1 mRNA and protein levels were increased in bladder cancer tissues and significantly correlated with N stage, T stage,and degree of tumor invasion. The expression of KPNB1 could effectively distinguish bladder cancer tissues from normal tissues (area under the curve=0.758). KPNB1 expression was higher in patients with poor progression-free survival. The proliferation and migration of T24 cells were significantly increased in the KPNB1 overexpressing group (P<0.05), and the proliferation and migration of T24 cells were significantly decreased in the KPNB1 knockdown group (P<0.05). The expression of STAT3/LDHA in T24 cells was relatively reduced in the KPNB1 knockdown group (P<0.05), and the expression of STAT3/LDHA in KPNB1 overexpressing T24 cells was significantly increased (P<0.05). After treating T24 cells in the KPNB1 overexpressing group with the STAT3 inhibitor Stattic, the expression of LDHA significantly decreased(P<0.05).

Conclusion

KPNB1 is significantly highly expressed in bladder cancer, which is of great diagnostic and prognostic value. KPNB1 plays a role in bladder cancer by participating in the STAT3/LDHA signaling pathway.

Key words: Bladder cancer, Karyopherin β1, Bioinformatics, STAT3/LDHA signaling pathway

Hongsheng Ji, Wanqing Wei, Jianguo Qiu, Liucheng Wang, Fujin Jiang, Xianyun Zhang, Sugui Wang. Expression of KPNB1 in bladder cancer and its role in proliferation and migration of bladder cancer cells[J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(11): 1044-1053.

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Figures/Tables 12

References 29

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属性	分类依据
年龄	分为≥60岁组和＜60岁组
T分期	分为T1、T2、T3、T4期
N分期	分为N0、N1期
M分期	分为M0、M1期
病理分级	分为StageⅠ、StageⅡ、StageⅢ、
StageⅣ组	StageⅣ组
肿瘤最大直径	分为＜3cm组和≥3cm组
人种	分为白种人、亚裔人和非亚裔人
治疗结果	分为疾病进展、部分缓解、疾病稳定、完全缓解组
KPNB1 mRNA中位表达量	分为高表达组和低表达组

属性	分类依据
年龄	分为≥60岁组和＜60岁组
T分期	分为T1、T2、T3、T4期
N分期	分为N0、N1期
M分期	分为M0、M1期
病理分级	分为StageⅠ、StageⅡ、StageⅢ、
StageⅣ组	StageⅣ组
肿瘤最大直径	分为＜3cm组和≥3cm组
人种	分为白种人、亚裔人和非亚裔人
治疗结果	分为疾病进展、部分缓解、疾病稳定、完全缓解组
KPNB1 mRNA中位表达量	分为高表达组和低表达组

临床病理特征	KPNB1低表达（206例）	KPNB1高表达（213例）	P值
T分期			＜0.001
T1期	124（29.7）	84（20.1）
T2期	56（13.4）	96（22.8）
T3期	22（5.3）	27（6.5）
T4期	4（0.9）	6（1.3）
N分期^a			＜0.001
N0期	169（43.9）	155（40.4）
N1期	22（5.4）	42（10.3）
M分期^a			0.054
M0期	177（45.1）	191（48.8）
M1期	17（4.2）	8（1.9）
病理分级^a			＜0.001
StageⅠ	82（21.3）	59（15.2）
StageⅡ	70（17.7）	58（14.9）
StageⅢ	38（9.3）	73（18.9）
StageⅣ	4（1.0）	7（1.7）
肿瘤最大直径^a			0.552
＜3cm	109（28.8）	94（22.5）
≥3cm	84（20.1）	108（28.6）
年龄			0.735
≤60	岁88（21.6）	91（22.3）
＞60	岁118（27.7）	122（28.4）

临床病理特征	KPNB1低表达（206例）	KPNB1高表达（213例）	P值
T分期			＜0.001
T1期	124（29.7）	84（20.1）
T2期	56（13.4）	96（22.8）
T3期	22（5.3）	27（6.5）
T4期	4（0.9）	6（1.3）
N分期^a			＜0.001
N0期	169（43.9）	155（40.4）
N1期	22（5.4）	42（10.3）
M分期^a			0.054
M0期	177（45.1）	191（48.8）
M1期	17（4.2）	8（1.9）
病理分级^a			＜0.001
StageⅠ	82（21.3）	59（15.2）
StageⅡ	70（17.7）	58（14.9）
StageⅢ	38（9.3）	73（18.9）
StageⅣ	4（1.0）	7（1.7）
肿瘤最大直径^a			0.552
＜3cm	109（28.8）	94（22.5）
≥3cm	84（20.1）	108（28.6）
年龄			0.735
≤60	岁88（21.6）	91（22.3）
＞60	岁118（27.7）	122（28.4）

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