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

doi:10.18632/oncotarget.7736

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

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 language	English
Pages (from-to)	19723-19737
Number of pages	15
Journal	Oncotarget
Volume	7
Issue number	15
DOIs	https://doi.org/10.18632/oncotarget.7736
State	Published - 12 Apr 2016

Keywords

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

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10.18632/oncotarget.7736

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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

@article{67298ed5295b48d885a0ca9f4f18444f,

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

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.",

keywords = "CENPE, KIF14, MiR-6500-3p, NCAPG, miR-137",

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

note = "Funding Information: This work was supported by the Ministry of Science and Technology [MOST; 103-2911-I-010- 506, 102-2314-B-010-045, 102-2314-B-075-033, 103- 2314-B-075-035 and 102-2314-B-038-060-MY3], Veterans General Hospitals University System of Taiwan (VGHUST) Joint Research Program, Tsou's Foundation [VGHUST103-G7-2-3], National Health Research Institutes [NHRI-EX103-10254SI], Taipei City Hospital [10401-62-014], National Science Council [102-2911- I-010-503, 101-2320-B-010-059-MY3], National Yang-Ming University [Ministry of Education, Aim for the Top University Plan], Veterans General Hospital Grant [V102-C-126], Taipei Medical University Hospital Grant [No.104 TMU-TMUH-11] and Health and Welfare Surcharge of Tobacco Products [MOHW105- TDU-B-212-134-001]. This work was also supported in part by the UST-UCSD International Center for Excellence in Advanced Bioengineering sponsored by the Taiwan MOST I-RiCE Program [103-2911-I-009-101].",

year = "2016",

month = apr,

day = "12",

doi = "10.18632/oncotarget.7736",

language = "English",

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TY - JOUR

T1 - Downregulation of miR-137 and miR-6500-3p promotes cell proliferation in pediatric high-grade gliomas

AU - Liang, Muh Lii

AU - Hsieh, Tsung Han

AU - Ng, Kim Hai

AU - Tsai, Ya Ni

AU - Tsai, Cheng Fong

AU - Chao, Meng En

AU - Liu, Da Jung

AU - Chu, Shing Shiung

AU - Chen, Wan

AU - Liu, Yun Ru

AU - Liu, Ren Shyan

AU - Lin, Shih Chieh

AU - Ho, Donald Ming Tak

AU - Wong, Tai Tong

AU - Yang, Muh Hwa

AU - Wang, Hsei Wei

N1 - Funding Information: This work was supported by the Ministry of Science and Technology [MOST; 103-2911-I-010- 506, 102-2314-B-010-045, 102-2314-B-075-033, 103- 2314-B-075-035 and 102-2314-B-038-060-MY3], Veterans General Hospitals University System of Taiwan (VGHUST) Joint Research Program, Tsou's Foundation [VGHUST103-G7-2-3], National Health Research Institutes [NHRI-EX103-10254SI], Taipei City Hospital [10401-62-014], National Science Council [102-2911- I-010-503, 101-2320-B-010-059-MY3], National Yang-Ming University [Ministry of Education, Aim for the Top University Plan], Veterans General Hospital Grant [V102-C-126], Taipei Medical University Hospital Grant [No.104 TMU-TMUH-11] and Health and Welfare Surcharge of Tobacco Products [MOHW105- TDU-B-212-134-001]. This work was also supported in part by the UST-UCSD International Center for Excellence in Advanced Bioengineering sponsored by the Taiwan MOST I-RiCE Program [103-2911-I-009-101].

PY - 2016/4/12

Y1 - 2016/4/12

N2 - 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.

AB - 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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KW - KIF14

KW - MiR-6500-3p

KW - NCAPG

KW - miR-137

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U2 - 10.18632/oncotarget.7736

DO - 10.18632/oncotarget.7736

M3 - Article

C2 - 26933822

AN - SCOPUS:84964727099

SN - 1949-2553

VL - 7

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JO - Oncotarget

JF - Oncotarget

IS - 15

ER -

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

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Keywords

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