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Cited by 99MicroRNA in disease regulationCancer-related molecular mechanisms researchGlioma Diagnosis and Treatment

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

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Li, X, Liu, Y, Granberg, K J, Wang, Q, Moore, L M, Ji, P, Gumin, J, Sulman, E P +7 more·2015·Oncogene
DOI 10.1038/onc.2014.98PMC PMC4205227
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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.

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  • The CDKN2A/ARF locus is frequently co-deleted with mir-491, which reduces glioblastoma cell invasion and proliferation.

    “The CDKN2A/ARF locus is frequently co-deleted with mir-491, which has been shown to reduce GBM cell invasion and proliferation.”

    From The p53 Pathway in Glioblastoma (2018) · cites this paper as [54]

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Authors
Li, X., Liu, Y., Granberg, K. J., Wang, Q., Moore, L. M., Ji, P., Gumin, J., Sulman, E. P., Calin, G. A., Haapasalo, H., Nykter, M., Shmulevich, I., Fuller, G. N., Lang, F. F., & Zhang, W.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • State Key Laboratory of Cancer Biology (CN)
  • Fimlab (Finland) (FI)
  • Tampere University of Technology (FI)
Corresponding author
Zhang, W
ORCID
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
2014-04-21
Volume
34
Issue
13
Pages
1619-1628
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
DOI
10.1038/onc.2014.98
PMC
PMC4205227
OpenAlex
W2048942013
Cited by
99
References
57
Citations by year
2025: 3 · 2024: 2 · 2023: 3 · 2022: 18 · 2021: 9 · 2020: 5 · 2019: 3 · 2018: 11 · 2017: 13 · 2016: 14 · 2015: 14 · 2014: 4
FWCI
4.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Cancer Society
  • Fourth Military Medical University
  • University of Texas MD Anderson Cancer Center
  • National Cancer Institute (CA115729, CA143835, CA141432, CA127001, R01CA141432, R56CA098503, CA098503, R01CA115729, R01CA098503, U24CA143835, P30CA016672, P50CA127001)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
Keywords
miR-491-5p, glioblastoma, CDKN2A, chromosome 9p21.3, tumor suppressor microRNA, EGFR, CDK6, Bcl-xL, IGFBP-2, glioma invasion, glioma stem cells, cell proliferation, cancer hallmarks
MeSH terms
Animals, Brain Neoplasms, Glioblastoma, Humans, Male, Neoplasm Invasiveness, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Insulin-Like Growth Factor Binding Protein 2, MicroRNAs, Cell Line, Tumor, bcl-X Protein, Cyclin-Dependent Kinase 6, Mice, ErbB Receptors

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