Abstract
Malignant gliomas are the most common and lethal intracranial tumors; differentiation therapy is a promising candidate for their treatment. In order to reveal the mechanisms related to glioma differentiation, after confirming that differentiation was induced by sodium phenylbutyrate in SHG-44 human glioma cells, RNA arbitrary primer differential display was used to screen differentially expressed genes. One gene was found to be upregulated by differential display, and this was also confirmed by reverse northern blot and quantitative real-time PCR analysis. After it was cloned and sequenced, the 505-bp fragment was identified as the MIBP1 (c-myc intron-binding protein 1) gene, also named Hivep2/MBP-2/Schnurri-2. Quantitative real-time PCR analysis of 30 human tissue samples revealed that the expression of MIBP1 tended to decrease with increasing WHO grade and was significantly depressed in the high malignancy gliomas group (WHO grade IV). We cloned and sequenced the MIBP1 gene, which was accepted by GenBank as number DQ231041. Finally, transfection of MIBP1 in a reverse transcription vector into glioma cells inhibited cell growth, induced differentiation, and blocked the cell cycle. Here, we identify and describe the structure and function of a differentiation-related gene, human MIBP1, in human glioma.
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References
Campbell DB, Levitt P (2003) Regionally restricted expression of the transcription factor c-myc intron 1 binding protein during brain development. J Comp Neurol 467(4):581–592
Chandana SR, Movva S, Arora M et al (2008) Primary brain tumors in adults. Am Fam Physician 77(10):1423–1430
Darefsky AS, King JT Jr, Dubrow R (2012) Adult glioblastoma multiforme survival in the temozolomide era: a population-based analysis of surveillance, epidemiology, and end results registries. Cancer 118(8):2163–2172
Du ZW (1984) Establishment of human malignant glioma cell line (SHG-44) and observation on its characteristics. Zhonghua Zhong Liu Za Zhi 6(4):241–243, Chinese
Fueyo J, Gomez-Manzano C, Yung WK (2011) Advances in translational research in neuro-oncology. Arch Neurol 68(3):303–308
Furnari FB, Fenton T, Bachoo RM et al (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21(21):2683–2710
Gilbert J, Baker SD, Bowling MK et al (2001) A phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies. Clin Cancer Res 7(8):2292–2300
Gore SD, Carducci MA (2000) Modifying histones to tame cancer: clinical development of sodium phenylbutyrate and other histone deacetylase inhibitors. Expert Opin Investig Drugs 9(12):2923–2934
Hadziahmetovic M, Shirai K, Chakravarti A (2011) Recent advancements in multimodality treatment of gliomas. Future Oncol 7(10):1169–1183
Iwashita Y, Fukuchi N, Waki M et al (2012) Genome-wide repression of NF-κB target genes by transcription factor MIBP1 and its modulation by O-linked β-N-acetylglucosamine (O-GlcNAc) transferase. J Biol Chem 287(13):9887–9900
Jiang Y, Uhrbom L (2012) On the origin of glioma. Ups J Med Sci 117(2):113–121
Li XN, Du ZW, Huang Q (1996) Modulation effects of hexamethylene bisacetamide on growth and differentiation of cultured human malignant glioma cells. J Neurosurg 84(5):831–838
Li XN, Du ZW, Huang Q et al (1997) Growth-inhibitory and differentiation-inducing activity of dimethylformamide in cultured human malignant glioma cells. Neurosurgery 40(6):1250–1259
Li XN, Parikh S, Shu Q et al (2004) Phenylbutyrate and phenylacetate induce differentiation and inhibit proliferation of human medulloblastoma cells. Clin Cancer Res 10(3):1150–1159
Liu Y, Rao MS (2004) Glial progenitors in the CNS and possible lineage relationships among them. Biol Cell 96(4):279–290
Lizardi PM, Forloni M, Wajapeyee N (2011) Genome-wide approaches for cancer gene discovery. Trends Biotechnol 29(11):558–568
Louis DN, Ohgaki H, Wiestler OD et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(5):97–109
Mou L, Miller H, Li J et al (1994) Improvements to the differential display method for gene analysis. Biochem Biophys Res Commun 199(2):564–569
Mugrauer G, Alt FW, Ekblom P (1988) N-myc proto-oncogene expression during organogenesis in the developing mouse as revealed by in situ hybridization. J Cell Biol 107(4):1325–1335
Nagao M, Saita Y, Hanyu R et al (2011) Schnurri-2 deficiency counteracts against bone loss induced by ovariectomy. J Cell Physiol 226(3):573–578
Nakayama T, Kimura MY (2010) Memory Th1/Th2 cell generation controlled by Schnurri-2. Adv Exp Med Biol 684:1–10
Orita M, Iwahana H, Kanazawa H et al (1989) Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci U S A 86(8):2766–2770
Pierce GB, Speers WC (1988) Tumors as caricatures of the process of tissue renewal: prospects for therapy by directing differentiation. Cancer Res 48(8):1996–2004
Reinhold W, Emens L, Itkes A et al (1995) The myc intron-binding polypeptide associates with RFX1 in vivo and binds to the major histocompatibility complex class II promoter region, to the hepatitis B virus enhancer, and to regulatory regions of several distinct viral genes. Mol Cell Biol 15(6):3041–3048
Samid D, Hudgins WR, Shack S et al (1997) Phenylacetate and phenylbutyrate as novel, nontoxic differentiation inducers. Adv Exp Med Biol 400A:501–505
Schneider T, Mawrin C, Scherlach C et al (2010) Gliomas in adults. Dtsch Arztebl Int 107(45):799–807
Shukla A, Malik M, Cataisson C et al (2009) TGF-beta signaling is regulated by Schnurri-2-dependent nuclear translocation of CLIC4 and consequent stabilization of phospho-Smad2 and 3. Nat Cell Biol 11(6):777–784
Staton TL, Lazarevic V, Jones DC et al (2011) Dampening of death pathways by schnurri-2 is essential for T-cell development. Nature 472(7341):105–109
Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996
Takagi T, Jin W, Taya K et al (2006) Schnurri-2 mutant mice are hypersensitive to stress and hyperactive. Brain Res 1108(1):88–97
Van Meir EG, Hadjipanayis CG, Norden AD et al (2010) Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin 60(3):166–193
van’t Veer LJ, Lutz PM, Isselbacher KJ et al (1992) Structure and expression of major histocompatibility complex-binding protein 2, a 275-kDa zinc finger protein that binds to an enhancer of major histocompatibility complex class I genes. Proc Natl Acad Sci U S A 89(19):8971–8975
Welsh J, Chada K, Dalal SS et al (1992) Arbitrary primed PCR fingerprinting of RNA. Nucleic Acids Res 20(19):4965–4970
Yamashita J, Iwamura C, Mitsumori K et al (2012) Murine Schnurri-2 controls natural killer cell function and lymphoma development. Leuk Lymphoma 53(3):479–486
Zajac-Kaye M, Ben-Baruch N, Kastanos E et al (2000) Induction of Myc-intron-binding polypeptides MIBP1 and RFX1 during retinoic acid-mediated differentiation of haemopoietic cells. Biochem J 345(Pt 3):535–541
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This work was supported by grants from the Tianjin Municipal Science and Technology Commission (Grant number 033800911 and 12ZCDZSY17700).
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Sun, L., Chen, X., Jin, X. et al. Identification and Characterization of Human MIBP1 Gene in Glioma Cell Differentiation. J Mol Neurosci 52, 294–301 (2014). https://doi.org/10.1007/s12031-013-0144-z
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DOI: https://doi.org/10.1007/s12031-013-0144-z