核转运蛋白α2在胶质瘤中的表达及对其生物学行为的影响

Expression of karyopherin α2 and its effect on the biological behaviors of glioma

目的探讨核转运蛋白α2(KPNA2)在胶质瘤中的表达与临床意义以及KPNA2对胶质瘤细胞生物学活性的影响。方法收集脑星形胶质细胞瘤Ⅱ、Ⅲ、Ⅳ级各30例,癌周相对正常脑组织15例,qRT-PCR及免疫组化分析KPNA2的表达;制备KPNA2干扰质粒,并以慢病毒为载体转染进入胶质瘤细胞系U87、U251,CCK8、Ed U法检测KPNA2敲除后对细胞增殖的影响,Transwell小室法检测KPNA2对胶质瘤细胞迁移和侵袭的影响。结果KPAN2在胶质瘤中表达升高,表达量与胶质瘤WHO分级呈正相关(rs=0.559,P<0.001),与患者预后呈负相关(总生存率:χ~2=21.39,P<0.001;无进展生存率:χ~2=8.057,P=0.004)。KPNA2敲除后胶质瘤细胞系的增殖、迁移和侵袭能力均明显减弱。结论 KPNA2在胶质瘤的发生发展中具有重要作用,可能成为新的临床诊治的标记物和治疗靶点。

Objective To explore the clinical significance and biological effects of karyopherin α2( KPNA2) on glioma. Methods A total of 90 specimens of cerebral astrocytoma were collected,including WHO grades Ⅱ,Ⅲ and Ⅳ( 30 cases for each grade),and 15 normal peritumoral tissues served as controls. The expression of KPNA2 was detected with qRT-PCR and immunohistochemistry. After that,the lentiviruses expressing small hairpin RNAs( shRNAs) of KPNA2 were introduced into the U87 and U251 glioma cells. The effects of KPNA2-knockdown on the proliferation of glioma cells were detected with CCK8 and Ed U,and the effects on the cell migration and invasion were assessed with Transwell assay. Results KPAN2 was overexpressed in glioma tissues,and high level of KPNA2 was positively correlated with the WHO classification of glioma( rs= 0.559,P<0.001) and negatively correlated with the prognosis of patients( overall survival: χ^2= 21. 39,P < 0. 001; relapse-free survival: χ^2= 8. 057,P = 0. 004). In addition,KPNA2-knockdown significantly weakened the proliferation,migration and invasion of glioma cell lines U87 and U251.Conclusion KPNA2 plays an important role in the tumorigenesis and development of glioma and may serve as a novel biomarker or therapeutic target for clinical diagnosis and treatment.