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OBJECTIVE MicroRNAs (miRNAs) are short noncoding RNAs capable of exerting dramatic effects by postranscriptionally regulating numerous messenger RNA targets. Toll-like receptor-4 (TLR-4) activation by lipopolysaccharide (LPS) induces the expression of three miRNAs in myeloid cells. The aim of this study was to investigate the in vivo consequences of(More)
Processing of pre-miRNA through Dicer1 generates an miRNA duplex that consists of an miRNA and miRNA* strand. Despite the general view that miRNA*s have no functional role, we further investigated miRNA* species in 10 deep-sequencing libraries from mouse and human tissue. Comparisons of miRNA/miRNA* ratios across the miRNA sequence libraries revealed that(More)
Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-containing elements comprise a significant portion (8%) of the human genome and are likely vestiges of retroviral infections during primate evolution. Many of the HERVs present in human DNA have retained functional promoter, enhancer, and polyadenylation signals, and these regulatory(More)
BACKGROUND Expression levels of the cell surface glycoprotein, CD7, and the serine protease, elastase 2 (ELA2), in the leukemic cells of patients with chronic myeloid leukemia (CML) have been associated with clinical outcome. However, little is known about the mechanisms that underlie the variable expression of these genes in the leukemic cells. RESULTS(More)
The t(10;11)(p13-14;q14-21) translocation, giving rise to the CALM-AF10 fusion gene, is a recurrent chromosomal rearrangement observed in patients with poor prognosis acute myeloid leukemia (AML). Although splicing of the CALM-AF10 fusion transcripts has been described in AML patients, the contribution of different CALM and AF10 domains to in vivo(More)
By virtue of having multiple targets, a microRNA (miRNA) can have variable effects on oncogenesis by acting as tumor suppressor or oncogene in a context-dependent manner. Genome-wide epigenetic changes that occur in various cancers affect the transcription of many genes. Since the transcriptional regulation of miRNAs remains an unexplored field, it is still(More)
Although structurally unrelated, the human killer cell Ig-like (KIR) genes and the rodent lectin-like Ly49 genes serve similar functional roles in NK cells. Moreover, both gene families display variegated, monoallelic expression patterns established at the transcriptional level. DNA methylation has been shown to play an important role in maintenance of(More)
The kinase PRKD2 (protein kinase D) is a crucial regulator of tumor cell-endothelial cell communication in gastrointestinal tumors and glioblastomas, but its mechanistic contributions to malignant development are not understood. Here, we report that the oncogenic chaperone HSP90 binds to and stabilizes PRKD2 in human cancer cells. Pharmacologic inhibition(More)
The predominant NK receptors recognizing MHC class I molecules are encoded by the killer cell immunoglobulin-like (KIR) genes in primates and the Ly49 genes in rodents. In human NK cells, the KIR repertoire is maintained epigenetically at the level of transcription via DNA methylation of the promoter region. We have previously shown a role for epigenetic(More)