title: Potential roles for Gfi1 in the pathogenesis and proliferation of glioma.
abstract: Glioblastoma multiforme (GBM) is a major form of adult brain tumour with relatively poor prognosis and high mortality. Temozolomide (TMZ)-based chemotherapy following neurosurgery and radiotherapy has been suggested as the first line of treatment and is proven to effectively prolong overall survival and enhance patient quality of life. However, not all patients benefit from this treatment because of drug resistance. Even patients with TMZ-sensitive GBM may become resistant, which is partly due to the restoration of activity of the DNA repair enzyme O(6)-methylguanine-DNA-methyltransferase (MGMT); thus, patients cannot evade eventual tumour recurrence. The cellular activity of MGMT is the most important determinant of TMZ-resistance. However, some patients with a low level of activated MGMT are also TMZ-resistant. The aberrant expression of HOXA9, one of the 39 class I homeobox genes, is a marker of poor prognosis, and its level gradually increases with histologic malignant progression, shorter time to overall survival (OS) and free progression survival (FPS) in glioma patients, which further supports an oncogenic role for HOXA9 in gliomas. The HOXA9-PI3K signalling pathway is an important mechanism in GBM that is independent of MGMT promoter methylation status. The DNA binding sites of growth factor independent-1 (Gfi1) can overlap with the HOXA9 promoter through the "AATC" versus "GATT" core sequence. The competition for this binding site inhibits the expression of HOXA9 and induces different transcriptional outcomes, which suggests a new direction for investigation of the mechanism underlying targeted therapy of malignant gliomas.
authors: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Fourth Military Medical University, 17 Changle Western Road, Xi'an, PR China.
authors: Huiyong
authors: H
authors: Huang
authors: Yongsheng
authors: Y
authors: Xiang
authors: Baoyi
authors: B
authors: Su
authors: Wei
authors: W
authors: Xiong
authors: Xiang
authors: X
authors: Zhang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000473:pathology* / Q000503:physiopathology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C498275:GFI1 protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; C097899:homeobox protein HOXA9