Dong Chengyuan, Mi Ruifang, Jin Guishan, Zhou Yiqiang, Zhang Jin, Liu Fusheng
Brain Tumor Research Center, Beijing Neurosurgical Institute and Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, P.R. China.
Mol Med Rep. 2015 Aug;12(2):1824-8. doi: 10.3892/mmr.2015.3614. Epub 2015 Apr 15.
Gliomas are the most frequently occurring primary tumor in the brain. The most malignant form of glioma, glioblastoma multiforme (GBM), is characterized by rapid and invasive growth and is restricted to the central nervous system (CNS). The transforming growth factor β2 (TGFβ2)/small mothers against decapentaplegic (Smad) signaling pathway is important, not only in GBM cell metabolism and invasion, but also in GBM cell proliferation. However, the functions of the downstream mediators of the TGFβ2/Smads signaling pathway remain to be fully elucidated. In the present study, short hairpin (sh)RNA interference was used to specifically inhibit the expression of Smad2 and Smad3 in the TGFβ2/Smad signaling pathway to investigate the effects of shRNA on the proliferation of human GBM cells. The results demonstrated that knockdown of either Smad2 or Smad3 enhanced cellular proliferation. Additionally, the key target genes involved in GBM cell proliferation, induced by TGFβ2, were found to be dependent on Smad3, but not Smad2.
神经胶质瘤是脑部最常见的原发性肿瘤。神经胶质瘤最恶性的形式,即多形性胶质母细胞瘤(GBM),其特征是生长迅速且具有侵袭性,并且局限于中枢神经系统(CNS)。转化生长因子β2(TGFβ2)/抗五聚体蛋白母细胞(Smad)信号通路不仅在GBM细胞代谢和侵袭中起重要作用,而且在GBM细胞增殖中也起重要作用。然而,TGFβ2/Smads信号通路下游介质的功能仍有待充分阐明。在本研究中,使用短发夹(sh)RNA干扰特异性抑制TGFβ2/Smad信号通路中Smad2和Smad3的表达,以研究shRNA对人GBM细胞增殖的影响。结果表明,敲低Smad2或Smad3均可增强细胞增殖。此外,发现由TGFβ2诱导的参与GBM细胞增殖的关键靶基因依赖于Smad3,而不依赖于Smad2。