Sigala Ioanna, Tsamis Konstantinos I, Gousia Anna, Alexiou George, Voulgaris Spyridon, Giannakouros Thomas, Kyritsis Athanassios P, Nikolakaki Eleni
Laboratory of Biochemistry, Department of Chemistry, Aristotelian University, Thessaloniki, Greece.
Neurosurgical Institute, Medical School, University of Ioannina, Ioannina, Greece.
Tumour Biol. 2016 Jul;37(7):8699-707. doi: 10.1007/s13277-015-4738-7. Epub 2016 Jan 6.
Among factors regulating the splicing of major importance is serine/arginine protein kinase 1 (SRPK1) that phosphorylates SR splicing factors. SRPK1 is expressed in the mammalian central nervous system in a region- and neuron-specific manner. Based on previous observations that glial cells are practically devoid of SRPK1 and reports showing aberrant expression of SRPK1 in numerous tumors, but with conflicting roles, this study aims to investigate the expression of SRPK1 in glioma and its influence on tumor cell biological features. As shown by immunohistochemical analysis, malignant glioma cells express SRPK1 in glioblastomas with significant association between SRPK1 expression and patients' survival. SRPK1 expression was also significantly upregulated at the messenger RNA (mRNA) and protein level in glioma cell lines. Small interfering RNA-mediated downregulation of SRPK1 had little effect on cell viability, while it slightly enhanced the sensitivity of cells to killing by cisplatin. These results support the idea that at least in vitro, the effect of SRPK1 knockdown on the viability of glioma cell lines is rather limited, while the in vivo effects could be attributed to the modulation of angiogenesis by SRPK1.
在调节剪接的重要因素中，丝氨酸/精氨酸蛋白激酶1（SRPK1）可磷酸化SR剪接因子。SRPK1在哺乳动物中枢神经系统中以区域和神经元特异性方式表达。基于先前观察到神经胶质细胞几乎不含SRPK1，以及报告显示SRPK1在众多肿瘤中表达异常但作用相互矛盾，本研究旨在调查SRPK1在胶质瘤中的表达及其对肿瘤细胞生物学特性的影响。免疫组织化学分析显示，恶性胶质瘤细胞在胶质母细胞瘤中表达SRPK1，且SRPK1表达与患者生存率之间存在显著关联。SRPK1在胶质瘤细胞系的信使核糖核酸（mRNA）和蛋白质水平上也显著上调。小干扰RNA介导的SRPK1下调对细胞活力影响不大，而略微增强了细胞对顺铂杀伤的敏感性。这些结果支持以下观点：至少在体外，敲低SRPK1对胶质瘤细胞系活力的影响相当有限，而体内效应可能归因于SRPK1对血管生成的调节。
