Role of Meis1 in mitochondrial gene transcription of pancreatic cancer cells.

Pre-B-cell leukemia transcription factor (PBX)/three-amino-acid loop extension (TALE) class transcription factors [PBX1-4, Meis homeobox (Meis) 1-3, pbx/knotted 1 homeobox (Prep) 1, 2] are involved in tumorigenesis and metastasis. To investigate further the function of PBX/TALE class transcription factors, mRNA expression profile after downregulation of each mRNA expression by siRNA transfection in pancreatic cancer cell line, Panc-1, was examined. Downregulation of Meis1 resulted in downregulation of mitochondrial genes, but those of PBX1 and PBX2 did not. Quantitative reverse transcription polymerase chain reaction confirmed downregulation of mitochondrial genes by Meis1 siRNA transfection. Chromatin immunoprecipitation assay revealed the binding of Meis1 to the mitochondrial promoter region that contained the putative Meis1 binding site. Luciferase reporter assay showed the increase of luciferase activity of a construct containing the Meis1 binding site compared with that with shorter fragment without Meis1 binding region. These findings indicate that Meis1 works as a transcription factor for mitochondrial genes in pancreatic cancer cells.