Martinez-Olivera Ramon, Datsi Angeliki, Stallkamp Maren, Köller Manfred, Kohtz Isabelle, Pintea Bogdan, Gousias Konstantinos
Department of Neurosurgery and Neurotraumatology, BG University Hospital Bergmannsheil, 44789 Bochum, Germany.
Department of Laboratory for Neurosurgical Research, BG University Hospital Bergmannsheil, 44789 Bochum, Germany.
Oncotarget. 2018 Sep 11;9(71):33471-33481. doi: 10.18632/oncotarget.26033.
We have previously shown that the nucleocytoplasmic carrier karyopherin a2 (KPNA2) is overexpressed in glioblastoma multiforme (GBM) whereas its expression is inversely associated with patient prognosis. However, the promoting role of KPNA2 in gliomagenesis is still poorly understood. This study aims to further elucidate this role of KPNA2 in GBM models. From four different tested GBM cell lines, the U87MG showed the highest proliferation, low adherence and outgrowth in 3D clusters as well as the highest expression of KPNA2, all features conferring greater malignant behaviour. Silencing of KPNA2 via siRNA interference in those cells significantly decreased their proliferative capacity ( = 0.001). We further observed both a significant cell cycle phase arrest ( = 0.040) and the promoting of cellular apoptosis ( = 0.016) as well as a strong trend ( = 0.062) for an inhibition of nuclear import of c-Myc. This study confirms that a higher expression of KPNA2 in GBM is associated with a more malignant phenotype also in models. While increased expression of KPNA2 promotes proliferation and survival of GBM tumour cells, silencing of KPNA2 conferred a less malignant behaviour. Our results strongly suggest that silencing of KPNA2 may play an important role in modulation of malignant features of GBM cells.
我们之前已经表明，核质载体核转运蛋白a2（KPNA2）在多形性胶质母细胞瘤（GBM）中过表达，而其表达与患者预后呈负相关。然而，KPNA2在胶质瘤发生中的促进作用仍知之甚少。本研究旨在进一步阐明KPNA2在GBM模型中的这一作用。在四种不同测试的GBM细胞系中，U87MG表现出最高的增殖能力、低贴壁性以及在三维聚集体中的生长能力，同时KPNA2表达最高，所有这些特征都赋予了更强的恶性行为。通过小干扰RNA（siRNA）干扰在这些细胞中沉默KPNA2，显著降低了它们的增殖能力（P = 0.001）。我们进一步观察到细胞周期阶段显著停滞（P = 0.040）、细胞凋亡增加（P = 0.016）以及c-Myc核输入抑制的强烈趋势（P = 0.062）。本研究证实，在GBM模型中，KPNA2的高表达也与更恶性的表型相关。虽然KPNA2表达增加促进了GBM肿瘤细胞的增殖和存活，但沉默KPNA2则赋予了较低的恶性行为。我们的结果强烈表明，沉默KPNA2可能在调节GBM细胞的恶性特征中发挥重要作用。
