GFI-1 overexpression promotes cell proliferation and apoptosis resistance in mycosis fungoides by repressing Bax and P21
Free PMC article
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. The majority of patients with advanced stage MF are resistant to conventional chemotherapy and thus have a poor prognosis. The transcriptional repressor growth factor independence-1 (GFI-1) serves an important role in the development of T-cells. The results of the present study demonstrated that the expression of GFI-1 at different clinical stages of MF was significantly higher compared with benign inflammatory dermatoses, and there was a significant association with disease progression. Gene knockdown of GFI-1 results in the inhibition of Hut-78 cell proliferation and clone formation in vitro, cell cycle arrest and spontaneous apoptosis, upregulation of cell cycle-related P21, as well as the apoptosis-related proteins Bax and Caspase-3, and downregulation of CDK2. Using luciferase assays, and mutational analysis, it was demonstrated that GFI-1 directly regulated the transcription of P21. The results of the present study highlighted a potential molecular therapeutic approach for the treatment of advanced MF.
Keywords: Bax; GFI-1; Hut-78; P21; mycosis fungoides.