Identification of the proliferative effect of Smad2 and 3 in the TGF β2/Smad signaling pathway using RNA interference in a glioma cell line

Dong,Chengyuan; Mi,Ruifang; Jin,Guishan; Zhou,Yiqiang; Zhang,Jin; Liu,Fusheng

doi:10.3892/mmr.2015.3614

Identification of the proliferative effect of Smad2 and 3 in the TGF β2/Smad signaling pathway using RNA interference in a glioma cell line

Authors:
- Chengyuan Dong
- Ruifang Mi
- Guishan Jin
- Yiqiang Zhou
- Jin Zhang
- Fusheng Liu
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Affiliations: Brain Tumor Research Center, Beijing Neurosurgical Institute and Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, P.R. China
Published online on: April 15, 2015 https://doi.org/10.3892/mmr.2015.3614
Pages: 1824-1828
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

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.

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1	Brat DJ, Scheithauer BW, Fuller GN and Tihan T: Newly codified glial neoplasms of the 2007 WHO Classification of Tumours of the Central Nervous System: angiocentric glioma, pilomyxoid astrocytoma and pituicytoma. Brain Pathol. 17:319–324. 2007. View Article : Google Scholar : PubMed/NCBI
2	Deorah S, Lynch CF, Sibenaller ZA and Ryken TC: Trends in brain cancer incidence and survival in the United States: Surveillance, Epidemiology, and End Results Program, 1973 to 2001. Neurosurg Focus. 20:E12006. View Article : Google Scholar : PubMed/NCBI
3	Eisele G and Weller M: Targeting apoptosis pathways in glioblastoma. Cancer Lett. 332:335–345. 2013. View Article : Google Scholar
4	Tanihara H, Inatani M and Honda Y: Growth factors and their receptors in the retina and pigment epithelium. Prog Retin Eye Res. 16:271–301. 1997. View Article : Google Scholar
5	Kjellman C, Olofsson SP, Hansson O, et al: Expression of TGF-beta isoforms, TGF-beta receptors, and Smad molecules at different stages of human glioma. Int J Cancer. 89:251–258. 2000. View Article : Google Scholar : PubMed/NCBI
6	Joseph JV, Balasubramaniyan V, Walenkamp A and Kruyt FA: TGF-beta as a therapeutic target in high grade gliomas- Promises and challenges. Biochem Pharmacol. 85:478–485. 2013. View Article : Google Scholar
7	Massagué J, Seoane J and Wotton D: Smad transcription factors. Genes Dev. 19:2783–2810. 2005. View Article : Google Scholar : PubMed/NCBI
8	Inman GJ and Hill CS: Stoichiometry of active smad-transcription factor complexes on DNA. J Biol Chem. 277:51008–51016. 2002. View Article : Google Scholar : PubMed/NCBI
9	Mishra L, Shetty K, Tang Y, Stuart A and Byers SW: The role of TGF-beta and Wnt signaling in gastrointestinal stem cells and cancer. Oncogene. 24:5775–5789. 2005. View Article : Google Scholar : PubMed/NCBI
10	Shi Y and Massagué J: Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 113:685–700. 2003. View Article : Google Scholar : PubMed/NCBI
11	Li J, Tang X and Chen X: Comparative effects of TGF-beta2/Smad2 and TGF-beta2/Smad3 signaling pathways on proliferation, migration, and extracellular matrix production in a human lens cell line. Exp Eye Res. 92:173–179. 2011. View Article : Google Scholar : PubMed/NCBI
12	Ungefroren H, Groth S, Sebens S, Lehnert H, Gieseler F and Fändrich F: Differential roles of Smad2 and Smad3 in the regulation of TGF-beta1-mediated growth inhibition and cell migration in pancreatic ductal adenocarcinoma cells: control by Rac1. Mol Cancer. 10:672011. View Article : Google Scholar
13	Bruna A, Darken RS, Rojo F, et al: High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell. 11:147–160. 2007. View Article : Google Scholar : PubMed/NCBI
14	Zheng W, Zhao X, Wang J and Lu L: Retinal vascular leakage occurring in GABA Rho-1 subunit deficient mice. Exp Eye Res. 90:634–640. 2010. View Article : Google Scholar : PubMed/NCBI
15	Feng C and Zuo Z: Regulatory factor X1-induced down-regulation of transforming growth factor beta2 transcription in human neuroblastoma cells. J Biol Chem. 287:22730–22739. 2012. View Article : Google Scholar : PubMed/NCBI
16	Schwartzbaum JA, Fisher JL, Aldape KD and Wrensch M: Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol. 2:494–503. 2006. View Article : Google Scholar : PubMed/NCBI
17	Stupp R, Mason WP, van den Bent MJ, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. Engl J Med. 352:987–996. 2005. View Article : Google Scholar
18	Tirado-Rodriguez B, Ortega E, Segura-Medina P and Huerta-Yepez S: TGF-β: An important mediator of allergic disease and a molecule with dual activity in cancer development. J Immunol Res. 2014:3184812014. View Article : Google Scholar
19	Der ynck R: Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 425:577–584. 2003. View Article : Google Scholar
20	Zhang L, Sato E, Amagasaki K, Nakao A and Naganuma H: Participation of an abnormality in the transforming growth factor-beta signaling pathway in resistance of malignant glioma cells to growth inhibition induced by that factor. J Neurosurg. 105:119–128. 2006. View Article : Google Scholar : PubMed/NCBI
21	Horst HA, Scheithauer BW, Kelly PJ and Kovach JS: Distribution of transforming growth factor-beta(1) in human astrocytomas. Hum Pathol. 23:1284–1288. 1992. View Article : Google Scholar : PubMed/NCBI
22	Dennler S, Huet S and Gauthier JM: A short amino-acid sequence in MH1 domain is responsible for functional differences between Smad2 and Smad3. Oncogene. 18:1643–1648. 1999. View Article : Google Scholar : PubMed/NCBI