Downregulation of SUN2, a novel tumor suppressor, mediates miR-221/222-induced malignancy in central nervous system embryonal tumors

Tsung Han Hsieh, Chen Li Chien, Yu Hsiu Lee, Chen I. Lin, Jui Yu Hsieh, Meng En Chao, Da Jung Liu, Shing Shiung Chu, Wan Chen, Shih Chieh Lin, Donald Ming Tak Ho, Ren Shyan Liu, Chi Hung Lin, Tai-Tong Wong, Hsei Wei Wang

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13 Citations (Scopus)

Abstract

Embryonal tumors of the central nervous system represent a highly malignant tumor group of medulloblastoma (MB), atypical teratoid/rhabdoid tumor (AT/RT) and primitive neuroectodermal tumor that frequently afflict children. AT/RT is often misdiagnosed as MB/primitive neuroectodermal tumor but with higher recurrence and lower survival rates. Pathogenesis of AT/ RT is largely unknown. In this study, we report both the miRNome and transcriptome traits in AT/RT and MB by using small RNA sequencing and gene expression microarray analyses. Our findings demonstrate that the miR-221/222-encoded micro RNAs are abundantly expressed in AT/RT but not in MB, which contribute substantially to the malignancy of embryonal tumors. miR-221/222 targeted SUN2, a newly discovered tumor suppressor, directly to increase cell proliferation and tumor malignancy in vitro and in vivo. Immunohistochemistry against SUN2 in a tissue microarray of 33 AT/RT and 154 MB tumor specimens also detected less SUN2 protein in AT/RT. Collectively, this study uncovers a novel tumor suppressor, SUN2, plays a critical role in miR-221/222-mediated AT/RT malignancy as well as supports miR-221/222 and SUN2 represent new promising targets for more active therapies in AT/ RT. In addition, our miRNome and transcriptome data also provide a roadmap for further embryonal tumor research.

Original languageEnglish
Pages (from-to)2164-2174
Number of pages11
JournalCarcinogenesis
Volume35
Issue number10
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research

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    Hsieh, T. H., Chien, C. L., Lee, Y. H., Lin, C. I., Hsieh, J. Y., Chao, M. E., Liu, D. J., Chu, S. S., Chen, W., Lin, S. C., Ho, D. M. T., Liu, R. S., Lin, C. H., Wong, T-T., & Wang, H. W. (2014). Downregulation of SUN2, a novel tumor suppressor, mediates miR-221/222-induced malignancy in central nervous system embryonal tumors. Carcinogenesis, 35(10), 2164-2174. https://doi.org/10.1093/carcin/bgu105