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Overexpression of iASPP-SV in glioma is associated with poor prognosis by promoting cell viability and antagonizing apoptosis

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Tumor Biology

Abstract

Inhibitor of apoptosis-stimulating protein of p53 (iASPP), encoded by PPP1R13L gene, is often overexpressed in human cancers. From the PPP1R13L gene, at least two isoforms, iASPP-L and iASPP-SV, are produced through alternative splicing. However, the role of these isoforms in glioma is still elusive. In this study, we examined the expression of iASPP-SV in astrocytic glioma tissues with different grades and normal human cerebral tissues. The result showed a higher messenger RNA (mRNA) expression level of iASPP-SV in astrocytic glioma patients with World Health Organization (WHO) grade II to IV in comparison to the normal controls. Additionally, mRNA expression level of iASPP-SV was gradually increased with the raise of the grade in glioma. High mRNA expression level of iASPP-SV was significantly associated with malignant WHO grades (P < 0.001). The protein expression level of iASPP-SV was consistent with the mRNA expression level. The Kaplan–Meier analysis revealed that high iASPP-SV mRNA expression significantly affected overall survival and progression-free survival (both P < 0.001). Furthermore, multivariate analysis indicated that the mRNA expression of iASPP-SV was an independent prognostic marker in glioma (P < 0.001). To further explore the role of iASPP-SV in glioma, U87 cells were transfected with iASPP-SV by lentivirus and then treated with temozolomide (TMZ). Overexpression of iASPP-SV promoted the cell viability and downregulated the expression of pro-apoptosis genes (Bax, Puma, p21, and Noxa) to inhibit apoptosis induced by TMZ. Our study provides the first evidence that high iASPP-SV expression may be a novel prognostic factor and therapeutic target for glioma.

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Acknowledgments

We thank Prof. Jianxiang Wang (Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College) for providing pCDH-iASPPsv plasmid and the packing plasmids. We thank Lei Wang (Beijing Tiantan Hospital, Capital Medical University), Zhaoke Zheng, and Kaiyuan Song (Beijing Tongren Hospital, Capital Medical University) for collecting some part of tissue samples. This work was supported by the National Natural Science Foundation of China (grant nos. 81000504, 81471209, 81171241), the Beijing Natural Science Foundation (grant no. 7132112), and Special Research Projects in Public Health and Welfare of China (grant no. 20142008-10).

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Authors and Affiliations

  1. Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China

    Xiangrong Liu, Fang Liu, Shaohong Wen, Kuan Liu, Yumin Luo & Xunming Ji

  2. Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Capital Medical University, Beijing, 100053, China

    Xiangrong Liu, Fang Liu, Shaohong Wen, Kuan Liu, Yumin Luo & Xunming Ji

  3. Department of Neurosurgery, Beijing Tongren Hospital, Capital Medical University, 1 Dong Jiao Min Xiang, Beijing, 100730, China

    Jun Kang & Shangfeng Zhao

  4. Department of Neurosurgery, The Affiliated Hospital of Weifang Medical College, Weifang, Shandong, 261031, China

    Xianwei Zeng & Kuan Liu

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  1. Xiangrong Liu
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Correspondence to Shangfeng Zhao.

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Liu, X., Kang, J., Liu, F. et al. Overexpression of iASPP-SV in glioma is associated with poor prognosis by promoting cell viability and antagonizing apoptosis. Tumor Biol. 37, 6323–6330 (2016). https://doi.org/10.1007/s13277-015-4503-y

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  • DOI: https://doi.org/10.1007/s13277-015-4503-y

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