Downregulation of MiR-137 and MiR-6500-3p Promotes Cell Proliferation in Pediatric High-grade Gliomas

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Mar 3

PMID 26933822

Citations 45

Authors

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

Affiliations

Soon will be listed here.

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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