![]() ![]() īecause STAT3 is constitutively activated in CLL cells and recent data demonstrated a global deregulation of the miR network in CLL, we hypothesized that STAT3 affects the expression of miRs in CLL cells. found that STAT3 activates the transcription of miR-21 and miR-181b-1, thereby inducing a stable transformed state in cancer cell lines. Although approximately 1000 microRNAs (miRs) collectively regulate more than 30% of protein-coding genes, little is known about miR gene transcription. However, protein-coding genes comprise only 3% of the human genome and only scant data are available on the role of STAT3 in the transcription of non-protein-coding genes. STAT3-induced transcription of protein-coding genes has been extensively studied in normal and neoplastic tissues. Furthermore, unphosphorylated STAT3, detected at high levels in CLL cells, constitutively activates the transcription factor nuclear factor κB, which is known to induce the production of several pro-inflammatory cytokines and activate survival pathways. Phosphoserine STAT3 shuttles to the nucleus, binds to DNA, and activates genes known to be activated by phosphotyrosine STAT3 in other cell types. #Vector td level 50 Activator#However, in almost all patients, regardless of their cytogenetic abnormalities, clinical characteristics, disease stage, or treatment status, signal transducer and activator of transcription 3 (STAT3) is constitutively phosphorylated on serine 727 residue. The presence of activated STAT3 has a profound effect on miR expression in CLL cells.ī-cell chronic lymphocytic leukemia (CLL) is characterized by asymmetrical proliferation and apoptosis of leukemia cells co-expressing the CD5 and CD19 antigens, and several chromosomal abnormalities, including del(13q), del(11q), del(17p), and trisomy 12, are detected in most, but not all, cases. qRT-PCR confirmed the array data in 5 of 6 miRs. Levels of 72 miRs were downregulated (n = 63) or upregulated (n = 9). We identified putative STAT3 binding sites in 160 promoter regions of 200 miRs, including miR-21, miR-29, and miR-155, whose levels have been reported to be upregulated in CLL. ![]() Then we transfected CLL cells with STAT3-shRNA or with an empty vector, and to determine which miRs are differentially expressed, we used a miR microarray approach followed by validation of the microarray results for 6 miRs using quantitative real-time polymerase chain reaction (qRT-PCR). We used publically available data from the ENCODE project to identify putative STAT3 binding sites in the promoters of miR genes. Because miR levels are deregulated in chronic lymphocytic leukemia (CLL) and signal transducer and activator of transcription (STAT)-3 is constitutively activated in CLL, we sought to determine whether STAT3 affects the transcription of miR genes in CLL cells. Approximately 1,000 microRNAs (miRs) are present in the human genome however, little is known about the regulation of miR transcription. ![]()
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