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Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) dysregulation in human malignant meningiomas

Oncogene volume 32, pages 1216–1222 (2013)Cite this article

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Abstract

Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) expression is often silenced in many types of human tumors. However, the relationship between RIZ1 expression and malignant meningiomas remains unclear. Here we have found for the first time that the expression of RIZ1 genes are associated with meningiomas progression through extensive analyses of Affymetrix GeneChip microarray data. Further validation methods for gene expression included quantitative PCR (qPCR), western blot and immunohistochemistry analysis, and these methods confirmed that RIZ1 is significantly downregulated in malignant meningioma tissues, as compared with benign meningiomas. In addition, malignant meningioma cells were stably transfected with ectogenic RIZ1 using Lentivirus-mediated transfection, and the transfections were followed by an in vitro 5-bromo-2-deoxyuridin incorporation assay, colony formation assay, cell cycle analysis, invasive analysis, apoptotic assay and western blot analysis. Our results demonstrate that the forced expression of RIZ1 in a malignant meningioma cell line inhibited cellular proliferation and arrested the cells in the G2/M phase of the cell cycle. We also confirmed that overexpression of RIZ1 may induce apoptosis of malignant meningioma cells. Furthermore, RIZ1 overexpression in malignant meningioma cells was associated with the downregulation of c-myc expression. These results from our study indicate that RIZ1 expression is significantly downregulated as the formation of meningiomas progressed, and suggest that RIZ1 may represent a promising candidate tumor suppressor gene that contributes to malignant meningiomas.

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Acknowledgements

The meningioma cell line IOMM-Lee and CH157-MN were kindly provided by Professor Randy Jensen and Dr David Gillespie (Utah State University, USA). The research was supported by Shanghai Science and Technology Foundation of China: 08431900400 (Guohan Hu), Shanghai Science and Technology Foundation of China: 09411950900 (Jianchun Liao), Shanghai Science and Technology Youth Fund of China: 09ZR410000 (Huanhai Liu) and Natural Sciences Fund Project of Anhui Province, China: No. 11040606M212 (Chunlin Wang).

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  1. Z Y Liu, J Y Wang and H H Liu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China

    Z Y Liu, J Y Wang, C L Wang, Y Q Tao, Y C Lu & G H Hu

  2. Department of Otorhinolaryngology (Head and Neck), Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China

    H H Liu & J C Liao

  3. Department of Pathology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China

    X M Ma

  4. Department of Neurosurgery, Hefei, Anhui, China

    C L Wang

  5. The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai, China

    X P Zhang

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Correspondence to J C Liao or G H Hu.

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Liu, Z., Wang, J., Liu, H. et al. Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) dysregulation in human malignant meningiomas. Oncogene 32, 1216–1222 (2013). https://doi.org/10.1038/onc.2012.155

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