Downregulation of miR-137 and miR-6500-3p promotes cell proliferation in pediatric high-grade gliomas

Muh Lii Liang, Tsung Han Hsieh, Kim Hai Ng, Ya Ni Tsai, Cheng Fong Tsai, Meng En Chao, Da Jung Liu, Shing Shiung Chu, Wan Chen, Yun Ru Liu, Ren Shyan Liu, Shih Chieh Lin, Donald Ming Tak Ho, Tai Tong Wong, Muh Hwa Yang, Hsei Wei Wang

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36 Citations (Scopus)

Abstract

Pediatric high-grade gliomas (pHGGs) are aggressive brain tumors affecting children, and outcomes have remained dismal, even with access to new multimodal therapies. In this study, we compared the miRNomes and transcriptomes of pediatric low- (pLGGs) and high-grade gliomas (pHGGs) using small RNA sequencing (smRNA-Seq) and gene expression microarray, respectively. Through integrated bioinformatics analyses and experimental validation, we identified miR-137 and miR-6500-3p as significantly downregulated in pHGGs. miR-137 or miR-6500-3p overexpression reduced cell proliferation in two pHGG cell lines, SF188 and UW479. CENPE, KIF14 and NCAPG levels were significantly higher in pHGGs than pLGGs, and were direct targets of miR-137 or miR-6500-3p. Furthermore, knockdown of CENPE, KIF14 or NCAPG combined with temozolomide treatment resulted in a combined suppressive effect on pHGG cell proliferation. In summary, our results identify novel mRNA/miRNA interactions that contribute to pediatric glioma malignancy and represent potential targets for the development of new therapeutic strategies.

Original languageEnglish
Pages (from-to)19723-19737
Number of pages15
JournalOncotarget
Volume7
Issue number15
DOIs
Publication statusPublished - Apr 12 2016

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Keywords

  • CENPE
  • KIF14
  • miR-137
  • MiR-6500-3p
  • NCAPG

ASJC Scopus subject areas

  • Oncology

Cite this

Liang, M. L., Hsieh, T. H., Ng, K. H., Tsai, Y. N., Tsai, C. F., Chao, M. E., Liu, D. J., Chu, S. S., Chen, W., Liu, Y. R., Liu, R. S., Lin, S. C., Ho, D. M. T., Wong, T. T., Yang, M. H., & Wang, H. W. (2016). Downregulation of miR-137 and miR-6500-3p promotes cell proliferation in pediatric high-grade gliomas. Oncotarget, 7(15), 19723-19737. https://doi.org/10.18632/oncotarget.7736