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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-03-26

AUTHORS

Xia Li, Yuexin Liu, Kirsi J Granberg, Qinhao Wang, Lynette M Moore, Ping Ji, Joy Gumin, Erik P Sulman, George A Calin, Hannu Haapasalo, Matti Nykter, Ilya Shmulevich, Gregory N Fuller, Frederick F Lang, Wei Zhang

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. More... »

PAGES

1619

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2014.98

DOI

http://dx.doi.org/10.1038/onc.2014.98

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1036831360

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24747968


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