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Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo

  • Authors:
    • Xuezhen Li
    • Xin He
    • Wei Tian
    • Jianzhen Wang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China, Department of Neurosurgery, Beijing Sanbo Brain Hospital, Capital Medical University, Beijing 100093, P.R. China, Department of Neurosurgery, Handan Central Hospital, Handan 056001, P.R. China, Department of Neurosurgery, General Hospital of Chinese People's Armed Police Forces, Beijing 100039, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 2843-2850
    |
    Published online on: October 15, 2014
       https://doi.org/10.3892/mmr.2014.2661
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Abstract

Notch signaling has been reported to be oncogenic or tumor suppressive, depending on the tissue context. To investigate the effects of Notch2 knockdown on U87 human glioma cell proliferation in vitro and in vivo, and the associated mechanisms, U87 cells were stably transfected with p green fluorescent protein (GFP)‑V‑RS Notch2 short hairpin (sh) RNA plasmid and pGFP‑V‑RS scramble‑shRNA plasmid. The former was referred to as the Notch2‑shRNA group and the latter as the negative‑shRNA group. mRNA and protein expression, cell proliferation, cell cycle and apoptosis were measured by reverse transcription‑polymerase chain reaction, western blot analysis, 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide analysis and flow cytometry using propidium iodide, respectively. Tumor volume, tumor weight and cumulative survival rate were determined in a nude mouse xenograft tumor model. Notch2 mRNA and protein expression in the Notch2‑shRNA group were reduced by 87.6 and 94.5% compared with the negative‑shRNA group (P<0.001). Notch2 knockdown significantly inhibited U87 cell proliferation after three days of culture (P<0.05). Notch2 silencing induced cell cycle arrest at G0/G1 phase by upregulation of p21 protein expression and downregulation of mini chromosome maintenance complex 2 and cyclin‑D1 protein expression. Furthermore, knockdown of Notch2 also induced U87 cell apoptosis. On day 50 after inoculation, tumor weight in the Notch2‑shRNA group was significantly lower than that in the negative‑shRNA group (0.55±0.10 vs. 1.23±0.52 g; P<0.01). The cumulative survival rate was significantly longer in the Notch2‑shRNA group compared with the negative‑shRNA group (log rank test P=0.01). In conclusion, Notch2 silencing inhibited U87 glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo. Thus, Notch2 may be a key therapeutic target for the treatment of glioma.
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1 

Wen PY and Kesari S: Malignant gliomas in adults. N Engl J Med. 359:492–507. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Louis DN: Molecular pathology of malignant gliomas. Annu Rev Pathol. 1:97–117. 2006. View Article : Google Scholar

3 

Hulleman E and Helin K: Molecular mechanisms in gliomagenesis. Adv Cancer Res. 94:1–27. 2005. View Article : Google Scholar

4 

Konopka G and Bonni A: Signaling pathways regulating gliomagenesis. Curr Mol Med. 3:73–84. 2003. View Article : Google Scholar

5 

Ohgaki H and Kleihues P: Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 64:479–489. 2005.

6 

Claus EB and Black PM: Survival rates and patterns of care for patients diagnosed with supratentorial low-grade gliomas: data from the SEER program, 1973–2001. Cancer. 106:1358–1363. 2006.PubMed/NCBI

7 

Anastas JN and Moon RT: WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer. 13:11–26. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Cerchia L, Martinez Montero JC and Monfared P: Signal transduction alterations in glioma: implications for diagnosis and therapy. J Signal Transduct. 2012:7042472012. View Article : Google Scholar : PubMed/NCBI

9 

Mellinghoff IK, Lassman AB and Wen PY: Signal transduction inhibitors and antiangiogenic therapies for malignant glioma. Glia. 59:1205–1212. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Chen J, Kesari S, Rooney C, et al: Inhibition of notch signaling blocks growth of glioblastoma cell lines and tumor neurospheres. Genes Cancer. 1:822–835. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Strizzi L, Hardy KM, Seftor EA, et al: Development and cancer: at the crossroads of Nodal and Notch signaling. Cancer Res. 69:7131–7134. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Purow BW, Haque RM, Noel MW, et al: Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation. Cancer Res. 65:2353–2363. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Pannuti A, Foreman K, Rizzo P, et al: Targeting Notch to target cancer stem cells. Clin Cancer Res. 16:3141–3152. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Sriuranpong V, Borges MW, Ravi RK, et al: Notch signaling induces cell cycle arrest in small cell lung cancer cells. Cancer Res. 61:3200–3205. 2001.PubMed/NCBI

15 

Ramdass B, Maliekal TT, Lakshmi S, et al: Coexpression of Notch1 and NF-kappaB signaling pathway components in human cervical cancer progression. Gynecol Oncol. 104:352–361. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Sjölund J, Johansson M, Manna S, et al: Suppression of renal cell carcinoma growth by inhibition of Notch signaling in vitro and in vivo. J Clin Invest. 118:217–228. 2008.PubMed/NCBI

17 

Fortini ME: Notch signaling: the core pathway and its posttranslational regulation. Dev Cell. 16:633–647. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Zardawi SJ, O’Toole SA, Sutherland RL and Musgrove EA: Dysregulation of Hedgehog, Wnt and Notch signalling pathways in breast cancer. Histol Histopathol. 24:385–398. 2009.PubMed/NCBI

19 

Ristorcelli E and Lombardo D: Targeting Notch signaling in pancreatic cancer. Expert Opin Ther Targets. 14:541–552. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Wang J, Wang C, Meng Q, et al: siRNA targeting Notch-1 decreases glioma stem cell proliferation and tumor growth. Mol Biol Rep. 39:2497–2503. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Dai J, Ma D, Zang S, et al: Cross-talk between Notch and EGFR signaling in human breast cancer cells. Cancer Invest. 27:533–540. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Noseda M, Chang L, McLean G, et al: Notch activation induces endothelial cell cycle arrest and participates in contact inhibition: role of p21Cip1 repression. Mol Cell Biol. 24:8813–8822. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Sarmento LM, Huang H, Limon A, et al: Notch1 modulates timing of G1-S progression by inducing SKP2 transcription and p27 Kip1 degradation. J Exp Med. 202:157–168. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Dakubo GD, Mazerolle CJ and Wallace VA: Expression of Notch and Wnt pathway components and activation of Notch signaling in medulloblastomas from heterozygous patched mice. J Neurooncol. 79:221–227. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Zhao N, Guo Y, Zhang M, et al: Akt-mTOR signaling is involved in Notch-1-mediated glioma cell survival and proliferation. Oncol Rep. 23:1443–1447. 2010.PubMed/NCBI

26 

Berry N, Gursel DB and Boockvar JA: Notch inhibition via micro-RNA blocks glioma development. Neurosurgery. 70:N20–N22. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Muto J, Imai T, Ogawa D, et al: RNA-binding protein Musashi1 modulates glioma cell growth through the post-transcriptional regulation of Notch and PI3 kinase/Akt signaling pathways. PLoS One. 7:e334312012. View Article : Google Scholar : PubMed/NCBI

28 

Palomero T and Ferrando A: Therapeutic targeting of NOTCH1 signaling in T-cell acute lymphoblastic leukemia. Clin Lymphoma Myeloma. 9(Suppl 3): S205–S210. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Mullendore ME, Koorstra JB, Li YM, et al: Ligand-dependent Notch signaling is involved in tumor initiation and tumor maintenance in pancreatic cancer. Clin Cancer Res. 15:2291–2301. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Sivasankaran B, Degen M, Ghaffari A, et al: Tenascin-C is a novel RBPJkappa-induced target gene for Notch signaling in gliomas. Cancer Res. 69:458–465. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Fan X, Mikolaenko I, Elhassan I, et al: Notch1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res. 64:7787–7793. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Chen L, Zhang R, Li P, et al: P53-induced microRNA-107 inhibits proliferation of glioma cells and down-regulates the expression of CDK6 and Notch-2. Neurosci Lett. 534:327–332. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Reichrath S, Müller CS, Gleissner B, et al: Notch- and vitamin D signaling in 1,25(OH)2D3-resistant glioblastoma multiforme (GBM) cell lines. J Steroid Biochem Mol Biol. 121:420–424. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Xu P, Yu S, Jiang R, et al: Differential expression of Notch family members in astrocytomas and medulloblastomas. Pathol Oncol Res. 15:703–710. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Xu P, Zhang A, Jiang R, et al: The different role of Notch1 and Notch2 in astrocytic gliomas. PLoS One. 8:e536542013. View Article : Google Scholar : PubMed/NCBI

36 

Xu P, Qiu M, Zhang Z, et al: The oncogenic roles of Notch1 in astrocytic gliomas in vitro and in vivo. J Neurooncol. 97:41–51. 2010. View Article : Google Scholar : PubMed/NCBI

37 

Jin R, Nakada M, Teng L, et al: Combination therapy using Notch and Akt inhibitors is effective for suppressing invasion but not proliferation in glioma cells. Neurosci Lett. 534:316–321. 2013. View Article : Google Scholar : PubMed/NCBI

38 

Rangarajan A, Hong SJ, Gifford A and Weinberg RA: Species- and cell type-specific requirements for cellular transformation. Cancer Cell. 6:171–183. 2004. View Article : Google Scholar : PubMed/NCBI

39 

Noseda M and Karsan A: Notch and minichromosome maintenance (MCM) proteins: integration of two ancestral pathways in cell cycle control. Cell Cycle. 5:2704–2709. 2006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li X, He X, Tian W and Wang J: Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo. Mol Med Rep 10: 2843-2850, 2014.
APA
Li, X., He, X., Tian, W., & Wang, J. (2014). Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo. Molecular Medicine Reports, 10, 2843-2850. https://doi.org/10.3892/mmr.2014.2661
MLA
Li, X., He, X., Tian, W., Wang, J."Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo". Molecular Medicine Reports 10.6 (2014): 2843-2850.
Chicago
Li, X., He, X., Tian, W., Wang, J."Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo". Molecular Medicine Reports 10, no. 6 (2014): 2843-2850. https://doi.org/10.3892/mmr.2014.2661
Copy and paste a formatted citation
x
Spandidos Publications style
Li X, He X, Tian W and Wang J: Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo. Mol Med Rep 10: 2843-2850, 2014.
APA
Li, X., He, X., Tian, W., & Wang, J. (2014). Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo. Molecular Medicine Reports, 10, 2843-2850. https://doi.org/10.3892/mmr.2014.2661
MLA
Li, X., He, X., Tian, W., Wang, J."Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo". Molecular Medicine Reports 10.6 (2014): 2843-2850.
Chicago
Li, X., He, X., Tian, W., Wang, J."Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo". Molecular Medicine Reports 10, no. 6 (2014): 2843-2850. https://doi.org/10.3892/mmr.2014.2661
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