MicroRNA profiles under ischemia-induced neovascularization were measured, the 3 downregulated miRNAs - 31, 150, and 184 were studied further. Injection of these miRNAs reduced angiogenesis in retinal cells, injection of-31, and -150 had the same effect on choroidal cells. Reporter assays validated targets for miR-31 (Pdgfb, Hif1a), and miR-150 (Pdgfb, Vegf) - all proangiogenic. Frizzled4 was identified bioinformatically as a target of miR-184. Induced VEGF expression, blockaded in AMD treatment, suppressed miR-150 while VEGF levels were also reduced by miR-31, possibly through HIF-1alpha, a transcriptional activator of VEGF.
[lab][cta]
Thursday, 29 May 2008
Cloning, characterization, and expression of microRNAs from the Asian malaria mosquito, Anopheles stephensi.
Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells
Constitutively active NF-kB is a functioning feature of many cancers.Mir-146a and miR-146b have been shown to downregulate 2 branches of the upstream cascade (IL-1 and Toll-like) through their repression of IRAK1 and TRAF6. In MDA-MB-231 cells ectopic expression of these miRNAs reduced phosphorylation of the inhibitor IkBa and NF-kB levels concomittantly by 70%. These cells showed a 80% and 60% loss of invasive capacity and migration respectively. siRNA-mediated inhibition of IkBa restored more than half of the NF-kB levels, indicating other pathways affected by these miRNAs to which end EGFR has also been identified as a target.
[cta][Oncogene][buck institute]
[cta][Oncogene][buck institute]
Isolation and characterization of CD146(+) multipotent mesenchymal stromal cells.
There is no good marker for mesenchymal stromal cells. A culture was selected on the basis of CD146. These were profiled for miRNA expression and a novel profile of differentiated chondrocytes was compared. Of 36 miRNAs altered a third were increased.Let-7 was the most significantly downregulated with pre-miR-204 at the top of the table.
[cte][lab][Exp. Haem.]
[cte][lab][Exp. Haem.]
The MYCN oncogene is a direct target of miR-34a
Elevated MYCN, seen in about 20-30% of neuroblastoma cases, is currently the only marker of disease progression - and characterizes it's most aggressive form. 1p36 deletions have been implicated in this cancer, as in others, but no single suppressor gene from this region has been found. Of 5 microRNAs mapping to this region miR-34a had the greatest effect on neuroblastoma cells, was complementary to MCYN 3'UTR at 2 locations, and mediated a profile of neural (GPCRs) rather than cell cycle genes. In 1p36 mutants, where mir-34a expression is lower, transfection causes an 80-90% reduction in MYCN.
[connotea],[CCR]
[connotea],[CCR]
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