RGD Reference Report - MicroRNA-21 promotes glioblastoma tumorigenesis by down-regulating insulin-like growth factor-binding protein-3 (IGFBP3). - Rat Genome Database

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MicroRNA-21 promotes glioblastoma tumorigenesis by down-regulating insulin-like growth factor-binding protein-3 (IGFBP3).

Authors: Yang, Chuan He  Yue, Junming  Pfeffer, Susan R  Fan, Meiyun  Paulus, Elena  Hosni-Ahmed, Amira  Sims, Michelle  Qayyum, Sohail  Davidoff, Andrew M  Handorf, Charles R  Pfeffer, Lawrence M 
Citation: Yang CH, etal., J Biol Chem. 2014 Sep 5;289(36):25079-87. doi: 10.1074/jbc.M114.593863. Epub 2014 Jul 24.
RGD ID: 152998875
Pubmed: PMID:25059666   (View Abstract at PubMed)
PMCID: PMC4155674   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M114.593863   (Journal Full-text)

Despite advances in surgery, imaging, chemotherapy, and radiation, patients with glioblastoma multiforme (GBM), the most common histological subtype of glioma, have an especially dismal prognosis; >70% of GBM patients die within 2 years of diagnosis. In many human cancers, the microRNA miR-21 is overexpressed, and accumulating evidence indicates that it functions as an oncogene. Here, we report that miR-21 is overexpressed in human GBM cell lines and tumor tissue. Moreover, miR-21 expression in GBM patient samples is inversely correlated with patient survival. Knockdown of miR-21 in GBM cells inhibited cell proliferation in vitro and markedly inhibited tumor formation in vivo. A number of known miR-21 targets have been identified previously. By microarray analysis, we identified and validated insulin-like growth factor (IGF)-binding protein-3 (IGFBP3) as a novel miR-21 target gene. Overexpression of IGFBP3 in glioma cells inhibited cell proliferation in vitro and inhibited tumor formation of glioma xenografts in vivo. The critical role that IGFBP3 plays in miR-21-mediated actions was demonstrated by a rescue experiment, in which IGFBP3 knockdown in miR-21KD glioblastoma cells restored tumorigenesis. Examination of tumors from GBM patients showed that there was an inverse relationship between IGFBP3 and miR-21 expression and that increased IGFBP3 expression correlated with better patient survival. Our results identify IGFBP3 as a novel miR-21 target gene in glioblastoma and suggest that the oncogenic miRNA miR-21 down-regulates the expression of IGFBP3, which acts as a tumor suppressor in human glioblastoma.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MIR21Humanbrain glioma  IEP human cells in mouse model and RNA:increased expression:brain (human)RGD 
Mir21Ratbrain glioma  ISOMIR21 (Homo sapiens)human cells in mouse model and RNA:increased expression:brain (human)RGD 
Mir21aMousebrain glioma  ISOMIR21 (Homo sapiens)human cells in mouse model and RNA:increased expression:brain (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir21  (microRNA 21)

Genes (Mus musculus)
Mir21a  (microRNA 21a)

Genes (Homo sapiens)
MIR21  (microRNA 21)


Additional Information