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PLoS One. 2014 Jan 23;9(1):e86102. doi: 10.1371/journal.pone.0086102. eCollection 2014.

The role of factor inhibiting HIF (FIH-1) in inhibiting HIF-1 transcriptional activity in glioblastoma multiforme.

Author information

  • 1Department of Biochemistry and Molecular Biology, Mayo Clinic Cancer Center, Rochester, Minnesota, United States of America.
  • 2Department of Neuro-Surgery, the First Affiliated Hospital of Baotou Medical College, Baotou, China.
  • 3Department of Biochemistry and Molecular Biology and Eppley Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
  • 4Department of Research and Development, Guangxi Medicinal Botanical Institute, Nanning, Guangxi, China.
  • 5Department of Radiation Oncology, Mayo Clinic Cancer Center, Rochester, Minnesota, United States of America.
  • 6Department of Biomedical Science, Mercer University School of Medicine, Savannah, Georgia, United States of America ; Department of Obstetrics and Gynecology, Memorial Health Hospital, Savannah, Georgia, United States of America.


Glioblastoma multiforme (GBM) accounts for about 38% of primary brain tumors in the United States. GBM is characterized by extensive angiogenesis induced by vascular growth factors and cytokines. The transcription of these growth factors and cytokines is regulated by the Hypoxia-Inducible-Factor-1(HIF-1), which is a key regulator mediating the cellular response to hypoxia. It is known that Factor Inhibiting HIF-1, or FIH-1, is also involved in the cellular response to hypoxia and has the capability to physically interact with HIF-1 and block its transcriptional activity under normoxic conditions. Delineation of the regulatory role of FIH-1 will help us to better understand the molecular mechanism responsible for tumor growth and progression and may lead to the design of new therapies targeting cellular pathways in response to hypoxia. Previous studies have shown that the chromosomal region of 10q24 containing the FIH-1 gene is often deleted in GBM, suggesting a role for the FIH-1 in GBM tumorigenesis and progression. In the current study, we found that FIH-1 is able to inhibit HIF-mediated transcription of GLUT1 and VEGF-A, even under hypoxic conditions in human glioblastoma cells. FIH-1 has been found to be more potent in inhibiting HIF function than PTEN. This observation points to the possibility that deletion of 10q23-24 and loss or decreased expression of FIH-1 gene may lead to a constitutive activation of HIF-1 activity, an alteration of HIF-1 targets such as GLUT-1 and VEGF-A, and may contribute to the survival of cancer cells in hypoxia and the development of hypervascularization observed in GBM. Therefore FIH-1 can be potential therapeutic target for the treatment of GBM patients with poor prognosis.

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