papers on microRNAs (computational, wetlab, clinical) http://www.citeulike.org/groupfunc/660 CiteULike.org en-gb Copyright © 2004-2007 Oversity Limited http://www.citeulike.org/group/660/article/4468964 MicroRNAs (miRNAs) are posttranscriptional modulators of gene expression and play an important role in many developmental processes. We report here that expression of microRNA-145 (miR-145) is low in self-renewing human embryonic stem cells (hESCs) but highly upregulated during differentiation. We identify the pluripotency factors OCT4, SOX2, and KLF4 as direct targets of miR-145 and show that endogenous miR-145 represses the 3' untranslated regions of OCT4, SOX2, and KLF4. Increased miR-145 expression inhibits hESC self-renewal, represses expression of pluripotency genes, and induces lineage-restricted differentiation. Loss of miR-145 impairs differentiation and elevates OCT4, SOX2, and KLF4. Furthermore, we find that the miR-145 promoter is bound and repressed by OCT4 in hESCs. This work reveals a direct link between the core reprogramming factors and miR-145 and uncovers a double-negative feedback loop involving OCT4, SOX2, KLF4, and miR-145. 2009-12-29T16:21:56+00:00 http://www.citeulike.org/group/660/article/5722551 
miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-α in human breast cancer cells

Cell Death and Differentiation advance online publication, September 4, 2009. doi:10.1038/cdd.2009.117

Authors: R Spizzo, M S Nicoloso, L Lupini, Y Lu, J Fogarty, S Rossi, B Zagatti, M Fabbri, A Veronese, X Liu, R Davuluri, C M Croce, G Mills, M Negrini
 & G A Calin 2009-12-25T03:21:40+00:00 http://www.citeulike.org/group/660/article/5156634 Increasing evidence has suggested that microRNAs (miRNA) play an important role in tumorigenesis. As transcriptional regulators, altered miRNA expression may affect many cancer-related biological pathways, indicating that miRNAs can function as tumor suppressors and/or oncogenes. We first performed a genetic association analysis by screening genetic variants in 15 miRNA genes and detected that a common sequence variant in hsa-miR-196a-2 (rs11614913, C[->]T) was significantly associated with decreased breast cancer risk (for homozygous variant: odds ratio, 0.44; 95% confidence interval, 0.28-0.70). Hypermethylation of a CpG island upstream (-700 bp) of the miR-196a-2 precursor was also associated with reduced breast cancer risk (odds ratio, 0.35; 95% confidence interval, 0.15-0.81). By delivering expression vectors containing either wild-type or mutant precursors of miR-196a-2 into breast cancer cells, we showed that this variant led to less efficient processing of the miRNA precursor to its mature form as well as diminished capacity to regulate target genes. A whole-genome expression microarray was done and a pathway-based analysis identified a cancer-relevant network formed by genes significantly altered following enforced expression of miR-196a-2. Mutagenesis analysis further showed that cell cycle response to mutagen challenge was significantly enhanced in cells treated with variant miR-196a-2 compared with cells treated with the wild-type. Taken together, our findings suggest that miR-196a-2 might have a potentially oncogenic role in breast tumorigenesis, and the functional genetic variant in its mature region could serve as a novel biomarker for breast cancer susceptibility. [Cancer Res 2009;69(14):5970-7] 10.1158/0008-5472.CAN-09-0236 2009-12-21T14:09:58+00:00 http://www.citeulike.org/group/660/article/5065718 In the past fifteen years, new classes of regulatory RNAs have been discovered, previously hidden in the transcriptome mostly due to their small size. These small regulatory RNAs include small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs). Numerous databases have been developed to store information about these small regulatory RNAs, and many tools have been developed to work with the data. This overview introduces the reader to the many resources available for working with small regulatory RNAs. 2009-12-21T13:14:11+00:00 http://www.citeulike.org/group/660/article/5090482 MicroRNAs (miRNAs) are regulators of myriad cellular events, but evidence for a single miRNA that can efficiently differentiate multipotent stem cells into a specific lineage or regulate direct reprogramming of cells into an alternative cell fate has been elusive. Here we show that miR-145 and miR-143 are co-transcribed in multipotent murine cardiac progenitors before becoming localized to smooth muscle cells, including neural crest stem-cell-derived vascular smooth muscle cells. miR-145 and miR-143 were direct transcriptional targets of serum response factor, myocardin and Nkx2-5 (NK2 transcription factor related, locus 5) and were downregulated in injured or atherosclerotic vessels containing proliferating, less differentiated smooth muscle cells. miR-145 was necessary for myocardin-induced reprogramming of adult fibroblasts into smooth muscle cells and sufficient to induce differentiation of multipotent neural crest stem cells into vascular smooth muscle. Furthermore, miR-145 and miR-143 cooperatively targeted a network of transcription factors, including Klf4 (Kruppel-like factor 4), myocardin and Elk-1 (ELK1, member of ETS oncogene family), to promote differentiation and repress proliferation of smooth muscle cells. These findings demonstrate that miR-145 can direct the smooth muscle fate and that miR-145 and miR-143 function to regulate the quiescent versus proliferative phenotype of smooth muscle cells. 2009-12-21T13:12:37+00:00