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

被引：70

作者：

Liang, Muh-Lii ^{[1
,2
]}

Hsieh, Tsung-Han ^{[3
,4
]}

Ng, Kim-Hai ^{[5
]}

Tsai, Ya-Ni ^{[5
]}

Tsai, Cheng-Fong ^{[6
]}

Chao, Meng-En ^{[7
,8
]}

Liu, Da-Jung ^{[2
]}

Chu, Shing-Shiung ^{[7
,8
]}

Chen, Wan ^{[7
,8
]}

Liu, Yun-Ru ^{[4
,9
]}

Liu, Ren-Shyan ^{[10
,11
,12
]}

Lin, Shih-Chieh ^{[13
]}

Ho, Donald Ming-Tak ^{[10
,13
]}

Wong, Tai-Tong ^{[2
,7
,8
,9
]}

Yang, Muh-Hwa ^{[1
,14
,15
,16
,17
,18
]}

Wang, Hsei-Wei ^{[1
,5
,6
,14
,15
]}

机构：

[1] Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan

[2] Taipei Vet Gen Hosp, Neurol Inst, Div Pediat Neurosurg, Taipei, Taiwan

[3] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Biol & Drug Discovery, Taipei, Taiwan

[4] Taipei Med Univ, Ctr Comprehens Canc, Taipei, Taiwan

[5] Natl Yang Ming Univ, Inst Microbiol & Immunol, Taipei 112, Taiwan

[6] Natl Yang Ming Univ, Inst Biomed Informat, Taipei 112, Taiwan

[7] Taipei Med Univ, Inst Clin Med, Taipei, Taiwan

[8] Taipei Med Univ, Taipei Med Univ Hosp, Dept Neurosurg, Taipei, Taiwan

[9] Taipei Med Univ, Off Human Res, Joint Biobank, Taipei, Taiwan

[10] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan

[11] Taipei Vet Gen Hosp, Dept Nucl Med, Natl PET Cyclotron Ctr, Taipei, Taiwan

[12] Natl Comprehens Mouse Phenotyping & Drug Testing, Taiwan Mouse Clin, Mol & Genet Imaging Core, Taipei, Taiwan

[13] Taipei Vet Gen Hosp, Dept Pathol & Lab Med, Taipei, Taiwan

[14] Natl Yang Ming Univ, Canc Res Ctr, Taipei 112, Taiwan

[15] Natl Yang Ming Univ, Genome Res Ctr, Taipei 112, Taiwan

[16] Taipei Vet Gen Hosp, Dept Med, Div Hematol Oncol, Taipei, Taiwan

[17] Natl Yang Ming Univ, Immun & Inflammat Res Ctr, Taipei 112, Taiwan

[18] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan

来源：

ONCOTARGET | 2016年 / 7卷 / 15期

关键词：

miR-137; miR-6500-3p; CENPE; KIF14; NCAPG; HUMAN HEPATOCELLULAR-CARCINOMA; MESSENGER-RNA EXPRESSION; SUPPRESSES TUMOR-GROWTH; FAMILY-MEMBER; 14; BREAST-CANCER; OVARIAN-CANCER; PROTEIN-E; CENP-E; MOLECULAR CLASSIFICATION; GLIOBLASTOMA-MULTIFORME;

D O I：

10.18632/oncotarget.7736

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：19723 / 19737

页数：15

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