Transcriptional down-regulation of IGFBP-3 in human hepatocellular carcinoma cells is mediated by the binding of TIA-1 to its AT-rich element in the 3'-untranslated region.
Insulin-like growth factor binding protein-3 (IGFBP-3) plays key roles in regulating cell growth, differentiation, and apoptosis in a variety of cellular systems. We have observed significant down-regulation of IGFBP-3 expression in primary human hepatocellular carcinoma (HCC) tissues when compared to adjacent histologically normal tissues. In this study, we functionally mapped the entire 3'-UTR of the IGFBP-3 mRNA, spanning 1471 nt and identified a 210 bp fragment consisting of AT-rich elements at the distal downstream region preceding the consensus pre-mRNA polyadenylation signal that provide high affinity binding for TIA-1 to mediate the specific suppression of IGFBP-3 expression in human HCC cells.
Subramaniam
Kothandharaman
K
Bek Chai Heah Laboratory of Cancer Genomics, Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, 11 Hospital Drive, Singapore.
Ooi
London Lucien P J
LL
Hui
Kam M
KM
D020413:3' Untranslated Regions; D020856:AT Rich Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D039102:Poly(A)-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000074019:T-Cell Intracellular Antigen-1; D014162:Transfection
D020413:3' Untranslated Regions; D018972:Insulin-Like Growth Factor Binding Protein 3; D039102:Poly(A)-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human