Cheng Gang, Zhang Leiming, Lv Wenying, Dong Chao, Wang Yaming, Zhang Jianning
Department of Neurosurgery, Navy General Hospital of PLA, 6 Fucheng Road, Haidian District, Beijing, 100048, China.
Med Oncol. 2015 Jan;32(1):439. doi: 10.1007/s12032-014-0439-0. Epub 2014 Dec 13.
Cyclin D1 has been reported overexpressed in many malignant cancers. However, the expression pattern and biological function of cyclin D1 in meningiomas are still unknown. In this study, we examined the expression of cyclin D1 in meningioma with immunohistochemistry and correlated the measure to the recurrence. Potential effects of cyclin D1 on tumor growth and apoptosis were also examined in representative cell lines (IOMM-Lee and CH157) by inhibiting cyclin D1 with RNA interference. We demonstrate that cyclin D1 mRNA and protein expression are positively correlated with meningioma grade and that higher cyclin D1 expression correlates with higher recurrence. Knockdown of cyclin D1 by the siRNA decreased IOMM-Lee and CH157 cell proliferation, promoted the rate of apoptosis and attenuated invasive capacity. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot analysis revealed that cells stably underexpressing cyclin D1 showed lower expression of survivin and the antiapoptotic protein B cell lymphoma-2 (Bcl-2) compared to control cells. These results indicate that high cyclin D1 expression is associated with a poor outcome of meningioma patients and knockdown of cyclin D1 expression may be a potential treatment for malignant meningioma.
据报道,细胞周期蛋白D1(Cyclin D1)在多种恶性肿瘤中过表达。然而,细胞周期蛋白D1在脑膜瘤中的表达模式和生物学功能仍不清楚。在本研究中,我们采用免疫组织化学方法检测了细胞周期蛋白D1在脑膜瘤中的表达,并将检测结果与复发情况相关联。我们还通过RNA干扰抑制细胞周期蛋白D1,在代表性细胞系(IOMM-Lee和CH157)中研究了其对肿瘤生长和凋亡的潜在影响。我们发现,细胞周期蛋白D1的mRNA和蛋白表达与脑膜瘤分级呈正相关,且细胞周期蛋白D1表达越高,复发率越高。通过小干扰RNA(siRNA)敲低细胞周期蛋白D1可降低IOMM-Lee和CH157细胞的增殖,提高凋亡率,并减弱侵袭能力。定量逆转录聚合酶链反应(qRT-PCR)和蛋白质免疫印迹分析显示,与对照细胞相比,稳定低表达细胞周期蛋白D1的细胞中生存素和抗凋亡蛋白B细胞淋巴瘤-2(Bcl-2)的表达较低。这些结果表明,细胞周期蛋白D1高表达与脑膜瘤患者的不良预后相关,敲低细胞周期蛋白D1的表达可能是恶性脑膜瘤的一种潜在治疗方法。