Two mature products of MIR-491 coordinate to suppress key cancer hallmarks in glioblastoma

X. Li, Y. Liu, K. J. Granberg, Q. Wang, L. M. Moore, Ping Ji, J. Gumin, E. P. Sulman, G. A. Calin, H. Haapasalo, M. Nykter, I. Shmulevich, G. N. Fuller, F. F. Lang, W. Zhang

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

MIR-491 is commonly co-deleted with its adjacent CDKN2A on chromosome 9p21.3 in glioblastoma multiforme (GBM). However, it is not known whether deletion of MIR-491 is only a passenger event or has an important role. Small-RNA sequencing of samples from GBM patients demonstrated that both mature products of MIR-491 (miR-491-5p and -3p) are downregulated in tumors compared with the normal brain. The integration of GBM data from The Cancer Genome Atlas (TCGA), miRNA target prediction and reporter assays showed that miR-491-5p directly targets EGFR, CDK6 and Bcl-xL, whereas miR-491-3p targets IGFBP2 and CDK6. Functionally, miR-491-3p inhibited glioma cell invasion; overexpression of both miR-491-5p and -3p inhibited proliferation of glioma cell lines and impaired the propagation of glioma stem cells (GSCs), thereby prolonging survival of xenograft mice. Moreover, knockdown of miR-491-5p in primary Ink4a-Arf-null mouse glial progenitor cells exacerbated cell proliferation and invasion. Therefore, MIR-491 is a tumor suppressor gene that, by utilizing both mature forms, coordinately controls the key cancer hallmarks: proliferation, invasion and stem cell propagation.

Original languageEnglish (US)
Pages (from-to)1619-1628
Number of pages10
JournalOncogene
Volume34
Issue number13
DOIs
StatePublished - Mar 26 2015
Externally publishedYes

Fingerprint

Glioblastoma
Glioma
Stem Cells
RNA Sequence Analysis
Neoplasms
Atlases
Tumor Suppressor Genes
MicroRNAs
Heterografts
Neuroglia
Down-Regulation
Chromosomes
Cell Proliferation
Genome
Cell Line
Brain

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Li, X., Liu, Y., Granberg, K. J., Wang, Q., Moore, L. M., Ji, P., ... Zhang, W. (2015). Two mature products of MIR-491 coordinate to suppress key cancer hallmarks in glioblastoma. Oncogene, 34(13), 1619-1628. https://doi.org/10.1038/onc.2014.98

Two mature products of MIR-491 coordinate to suppress key cancer hallmarks in glioblastoma. / Li, X.; Liu, Y.; Granberg, K. J.; Wang, Q.; Moore, L. M.; Ji, Ping; Gumin, J.; Sulman, E. P.; Calin, G. A.; Haapasalo, H.; Nykter, M.; Shmulevich, I.; Fuller, G. N.; Lang, F. F.; Zhang, W.

In: Oncogene, Vol. 34, No. 13, 26.03.2015, p. 1619-1628.

Research output: Contribution to journalArticle

Li, X, Liu, Y, Granberg, KJ, Wang, Q, Moore, LM, Ji, P, Gumin, J, Sulman, EP, Calin, GA, Haapasalo, H, Nykter, M, Shmulevich, I, Fuller, GN, Lang, FF & Zhang, W 2015, 'Two mature products of MIR-491 coordinate to suppress key cancer hallmarks in glioblastoma', Oncogene, vol. 34, no. 13, pp. 1619-1628. https://doi.org/10.1038/onc.2014.98
Li, X. ; Liu, Y. ; Granberg, K. J. ; Wang, Q. ; Moore, L. M. ; Ji, Ping ; Gumin, J. ; Sulman, E. P. ; Calin, G. A. ; Haapasalo, H. ; Nykter, M. ; Shmulevich, I. ; Fuller, G. N. ; Lang, F. F. ; Zhang, W. / Two mature products of MIR-491 coordinate to suppress key cancer hallmarks in glioblastoma. In: Oncogene. 2015 ; Vol. 34, No. 13. pp. 1619-1628.
@article{0573166f31b843b4b33ce44aebcce9e7,
title = "Two mature products of MIR-491 coordinate to suppress key cancer hallmarks in glioblastoma",
abstract = "MIR-491 is commonly co-deleted with its adjacent CDKN2A on chromosome 9p21.3 in glioblastoma multiforme (GBM). However, it is not known whether deletion of MIR-491 is only a passenger event or has an important role. Small-RNA sequencing of samples from GBM patients demonstrated that both mature products of MIR-491 (miR-491-5p and -3p) are downregulated in tumors compared with the normal brain. The integration of GBM data from The Cancer Genome Atlas (TCGA), miRNA target prediction and reporter assays showed that miR-491-5p directly targets EGFR, CDK6 and Bcl-xL, whereas miR-491-3p targets IGFBP2 and CDK6. Functionally, miR-491-3p inhibited glioma cell invasion; overexpression of both miR-491-5p and -3p inhibited proliferation of glioma cell lines and impaired the propagation of glioma stem cells (GSCs), thereby prolonging survival of xenograft mice. Moreover, knockdown of miR-491-5p in primary Ink4a-Arf-null mouse glial progenitor cells exacerbated cell proliferation and invasion. Therefore, MIR-491 is a tumor suppressor gene that, by utilizing both mature forms, coordinately controls the key cancer hallmarks: proliferation, invasion and stem cell propagation.",
author = "X. Li and Y. Liu and Granberg, {K. J.} and Q. Wang and Moore, {L. M.} and Ping Ji and J. Gumin and Sulman, {E. P.} and Calin, {G. A.} and H. Haapasalo and M. Nykter and I. Shmulevich and Fuller, {G. N.} and Lang, {F. F.} and W. Zhang",
year = "2015",
month = "3",
day = "26",
doi = "10.1038/onc.2014.98",
language = "English (US)",
volume = "34",
pages = "1619--1628",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "13",

}

TY - JOUR

T1 - Two mature products of MIR-491 coordinate to suppress key cancer hallmarks in glioblastoma

AU - Li, X.

AU - Liu, Y.

AU - Granberg, K. J.

AU - Wang, Q.

AU - Moore, L. M.

AU - Ji, Ping

AU - Gumin, J.

AU - Sulman, E. P.

AU - Calin, G. A.

AU - Haapasalo, H.

AU - Nykter, M.

AU - Shmulevich, I.

AU - Fuller, G. N.

AU - Lang, F. F.

AU - Zhang, W.

PY - 2015/3/26

Y1 - 2015/3/26

N2 - MIR-491 is commonly co-deleted with its adjacent CDKN2A on chromosome 9p21.3 in glioblastoma multiforme (GBM). However, it is not known whether deletion of MIR-491 is only a passenger event or has an important role. Small-RNA sequencing of samples from GBM patients demonstrated that both mature products of MIR-491 (miR-491-5p and -3p) are downregulated in tumors compared with the normal brain. The integration of GBM data from The Cancer Genome Atlas (TCGA), miRNA target prediction and reporter assays showed that miR-491-5p directly targets EGFR, CDK6 and Bcl-xL, whereas miR-491-3p targets IGFBP2 and CDK6. Functionally, miR-491-3p inhibited glioma cell invasion; overexpression of both miR-491-5p and -3p inhibited proliferation of glioma cell lines and impaired the propagation of glioma stem cells (GSCs), thereby prolonging survival of xenograft mice. Moreover, knockdown of miR-491-5p in primary Ink4a-Arf-null mouse glial progenitor cells exacerbated cell proliferation and invasion. Therefore, MIR-491 is a tumor suppressor gene that, by utilizing both mature forms, coordinately controls the key cancer hallmarks: proliferation, invasion and stem cell propagation.

AB - MIR-491 is commonly co-deleted with its adjacent CDKN2A on chromosome 9p21.3 in glioblastoma multiforme (GBM). However, it is not known whether deletion of MIR-491 is only a passenger event or has an important role. Small-RNA sequencing of samples from GBM patients demonstrated that both mature products of MIR-491 (miR-491-5p and -3p) are downregulated in tumors compared with the normal brain. The integration of GBM data from The Cancer Genome Atlas (TCGA), miRNA target prediction and reporter assays showed that miR-491-5p directly targets EGFR, CDK6 and Bcl-xL, whereas miR-491-3p targets IGFBP2 and CDK6. Functionally, miR-491-3p inhibited glioma cell invasion; overexpression of both miR-491-5p and -3p inhibited proliferation of glioma cell lines and impaired the propagation of glioma stem cells (GSCs), thereby prolonging survival of xenograft mice. Moreover, knockdown of miR-491-5p in primary Ink4a-Arf-null mouse glial progenitor cells exacerbated cell proliferation and invasion. Therefore, MIR-491 is a tumor suppressor gene that, by utilizing both mature forms, coordinately controls the key cancer hallmarks: proliferation, invasion and stem cell propagation.

UR - http://www.scopus.com/inward/record.url?scp=85003045383&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85003045383&partnerID=8YFLogxK

U2 - 10.1038/onc.2014.98

DO - 10.1038/onc.2014.98

M3 - Article

VL - 34

SP - 1619

EP - 1628

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 13

ER -