MIR

MicroRNAs (mirs) are small noncoding RNA molecules (∼22 nucleotides) that regulate posttranscriptional gene expression. Currently, there has not been a comprehensive study of their role in primary head and neck squamous cell carcinoma (HNSCC). To determine the role of mirs in HNSCC, we screened for altered microRNA expression in HNSCC primary tissue and cell lines. We then further tested the functional impact of alterations of specific mirs. An initial screening of 4 primary HNSCC, 4 normal mucosal controls and 4 HNSCC cell lines was analyzed for mature microRNA expression by microarray. Significance was determined using significance analysis of microarrays (SAM). Nine microRNAs were found by SAM to be upregulated or downregulated in tumor tissue including mir-21, let-7, 18, 29c, 142-3p, 155, 146b (overexpressed) and 494 (underexpressed). Mir-21 was validated by qRT-PCR. Functional validation by growth assays was performed, further validating mir-21. Transfection of mir-21 into JHU-011 and JHU-012 cell lines showed a 39% increase in cell growth at 72 hr relative to controls (p < 0.05). Transfection of the inhibitor into JHU-O12 cell lines showed a 92% decrease in cell growth relative to controls at 72 hr (p < 0.05). In addition, flow cytometry analysis of JHU-012 cells 48 hr after mir-21 inhibitor transfection showed a statistically significant increase in cytochrome c release and increased apoptosis. These differentially expressed microRNAs may be of interest as potential novel oncogenes and tumor suppressor genes in HNSCC. Mir-21 is a putative oncogenic microRNA in head and neck cancer. © 2008 Wiley-Liss, Inc.

The anti-inflammatory properties of the flavonol quercetin have been intensively investigated using in vitro cell systems and are to a great extent reflected by changes in the expression of inflammatory markers. However, information relating to the degree at which quercetin affects inflammatory gene expression in vivo is limited. Recently, micro RNAs (miRNAs) have been identified as powerful post-transcriptional gene regulators. The effect of quercetin on miRNA regulation in vivo is largely unknown. Laboratory mice were fed for six weeks with control or quercetin enriched high fat diets and biomarkers of inflammation as well as hepatic levels of miRNAs previously involved in inflammation (miR-125b) and lipid metabolism (miR-122) were determined. We found lower mRNA steady state levels of the inflammatory genes interleukin 6, C-reactive protein, monocyte chemoattractant protein 1, and acyloxyacyl hydrolase in quercetin fed mice. In addition we found evidence for an involvement of red...

This text offers a personal and very subjective view on the current situation of Music Information Research (MIR). Motivated by the desire to build systems with a somewhat deeper understanding of music than the ones we currently have, I try to sketch a number of challenges for the next decade of MIR research, grouped around six simple truths about music that are probably generally agreed on but often ignored in everyday research.

Valproic acid (VPA) exhibits important pharmacological properties but has been reported to trigger side effects, notably on the hematological system. We previously reported that VPA affects hematopoietic homeostasis by inhibiting erythroid differentiation and promoting myeloid and megakaryocyte differentiation. Here, we analyzed the effect of VPA on regulatory factors involved in erythro-megakaryocytic differentiation pathways, including transcription factors and microRNAs (miRs). We demonstrate that VPA inhibited erythroid differentiation in erythropoietin (Epo)-stimulated TF1 leukemia cells and CD34(+)/hematopoietic stem cells (HSCs) and in aclacinomycin-(Acla)-treated K562 cells. Mir-144/451 gene expression was decreased in all erythroid and megakaryocyte models in correlation with GATA-1 inhibition. In Epo-stimulated CD34(+)/HSCs, VPA induced the expression of the ETS family transcription factors PU.1, ETS-1, GABP-α, Fli-1 and GATA-2, which are all known to be negative regulator...