Abstract
B-cell chronic lymphocytic leukemia (CLL) is the most common human leukemia. 13q14 deletions are most common chromosomal alterations in CLL. We previously reported that miR-15/16 is a target of 13q14 deletions and plays a tumor suppressor role by targeting BCL2. Because DLEU7 is located near miR-15/16 and is also positioned within a minimal deleted region, we investigated whether DLEU7 could also play a tumor suppressor role. Recent studies of transgenic mouse models demonstrated the importance of the nuclear factor-kappaB (NF-kappaB) pathway in CLL. To examine the possible role of DLEU7 in CLL, we investigated the effect of DLEU7 expression on NF-kappaB and nuclear factor of activated T cells (NFAT) activity. We found that DLEU7 functions as a potent NF-kappaB and NFAT inhibitor by physically interacting and inhibiting TACI and BCMA, members of the tumor necrosis factor (TNF) receptor family involved in B-CLL. In addition, DLEU7 expression in A549 lung cancer cells resulted in a decrease in S phase and increased apoptosis. The results suggest that loss of DLEU7 may cooperate with the loss of miR-15/16 in the pathogenesis of CLL.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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B-Cell Maturation Antigen / genetics
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B-Cell Maturation Antigen / metabolism
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Blotting, Western
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Chromosomes, Human, Pair 13 / genetics*
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Fluorescent Antibody Technique
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Genes, Tumor Suppressor*
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Humans
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Immunoprecipitation
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Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
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Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
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Leukemia, Lymphocytic, Chronic, B-Cell / pathology
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Luciferases / metabolism
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MicroRNAs / physiology
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NF-kappa B / genetics
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NF-kappa B / metabolism
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NFATC Transcription Factors / metabolism
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Neoplasm Proteins
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S Phase
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Sequence Deletion*
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Transfection
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Transmembrane Activator and CAML Interactor Protein / genetics
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Transmembrane Activator and CAML Interactor Protein / metabolism
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
Substances
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B-Cell Maturation Antigen
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DLEU7 protein, human
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MIRN16 microRNA, human
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MicroRNAs
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NF-kappa B
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NFATC Transcription Factors
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Neoplasm Proteins
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TNFRSF13B protein, human
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TNFRSF17 protein, human
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Transmembrane Activator and CAML Interactor Protein
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Tumor Suppressor Proteins
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Luciferases