Oncotarget

Research Papers:

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 _ and Hsei-Wei Wang

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Oncotarget. 2016; 7:19723-19737. https://doi.org/10.18632/oncotarget.7736

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Abstract

Muh-Lii Liang1,2,*, Tsung-Han Hsieh3,4,*, Kim-Hai Ng5, Ya-Ni Tsai5, Cheng-Fong Tsai6, Meng-En Chao7,8, Da-Jung Liu2, Shing-Shiung Chu7,8, Wan Chen7,8, Yun-Ru Liu4,9, Ren-Shyan Liu10,11,12, Shih-Chieh Lin13, Donald Ming-Tak Ho10,13, Tai-Tong Wong2,7,8,9, Muh-Hwa Yang1,14,15,16,17 and Hsei-Wei Wang1,5,6,14

1 Institutes of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

2 Division of Pediatric Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan

3 PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

4 Comprehensive Cancer Center of Taipei Medical University, Taipei Medical University, Taipei, Taiwan

5 Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan

6 Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan

7 Institutes of Clinical Medicine, Taipei Medical University, Taipei, Taiwan

8 Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan

9 Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan

10 School of Medicine, National Yang-Ming University, Taipei, Taiwan

11 National PET/Cyclotron Center, Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

12 Molecular and Genetic Imaging Core/Taiwan Mouse Clinic National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, Taiwan

13 Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

14 Cancer Research Center & Genome Research Center, National Yang-Ming University, Taipei, Taiwan

15 Division of Hematology-Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

16 Immunity and Inflammation Research Center, National Yang-Ming University, Taipei, Taiwan

17 Genomic Research Center, Academia Sinica, Taipei, Taiwan

* These authors have contributed equally to this work

Correspondence to:

Muh-Hwa Yang, email:

Tai-Tong Wong, email:

Keywords: miR-137, miR-6500-3p, CENPE, KIF14, NCAPG

Received: December 15, 2015 Accepted: February 18, 2016 Published: February 25, 2016

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.


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