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Small hairpin RNA
About: Small hairpin RNA is a research topic. Over the lifetime, 9279 publications have been published within this topic receiving 285471 citations.
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TL;DR: KCa3.1 expression significantly enhances glioma invasion and that either specific pharmacological inhibition with TRAM‐34 or elimination of the channel impairs invasion, which suggests that KCa 3.1 represents a viable therapeutic target to reduce gliomas invasion.
Abstract: Glioblastoma multiforme are highly motile primary brain tumors. Diffuse tissue invasion hampers surgical resection leading to poor patient prognosis. Recent studies suggest that intracellular Ca(2+) acts as a master regulator for cell motility and engages a number of downstream signals including Ca(2+) -activated ion channels. Querying the REepository of Molecular BRAin Neoplasia DaTa (REMBRANDT), an annotated patient gene database maintained by the National Cancer Institute, we identified the intermediate conductance Ca(2+) -activated K(+) channels, KCa3.1, being overexpressed in 32% of glioma patients where protein expression significantly correlated with poor patient survival. To mechanistically link KCa3.1 expression to glioma invasion, we selected patient gliomas that, when propagated as xenolines in vivo, present with either high or low KCa3.1 expression. In addition, we generated U251 glioma cells that stably express an inducible knockdown shRNA to experimentally eliminate KCa3.1 expression. Subjecting these cells to a combination of in vitro and in situ invasion assays, we demonstrate that KCa3.1 expression significantly enhances glioma invasion and that either specific pharmacological inhibition with TRAM-34 or elimination of the channel impairs invasion. Importantly, after intracranial implantation into SCID mice, ablation of KCa3.1 with inducible shRNA resulted in a significant reduction in tumor invasion into surrounding brain in vivo. These results show that KCa3.1 confers an invasive phenotype that significantly worsens a patient's outlook, and suggests that KCa3.1 represents a viable therapeutic target to reduce glioma invasion.
82 citations
Patent•
05 Aug 2003TL;DR: In this article, a short interfering hairpin RNA with the structure X1-L-X2 was proposed, where X1 and X2 are nucleotide sequences having sufficient complementarity to one another to form a double-stranded stem hybrid and L is a loop region comprising a non-nucleotide linker molecule.
Abstract: This invention provides a short interfering hairpin RNA having the structure X1-L-X2, wherein X1 and X2 are nucleotide sequences having sufficient complementarity to one another to form a double-stranded stem hybrid and L is a loop region comprising a non-nucleotide linker molecule, wherein at least a portion of one of the nucleotide sequences located within the double-stranded stem is complementary to a sequence of said target RNA.
81 citations
TL;DR: The photocaging of a synthetic gene network using unnatural amino acid mutagenesis in mammalian cells was demonstrated with an engineered bacteriophage RNA polymerase, demonstrating tight spatial and temporal control.
Abstract: Photocaging provides a method to spatially and temporally control biological function and gene expression with high resolution. Proteins can be photochemically controlled through the site-specific installation of caging groups on amino acid side chains that are essential for protein function. The photocaging of a synthetic gene network using unnatural amino acid mutagenesis in mammalian cells was demonstrated with an engineered bacteriophage RNA polymerase. A caged T7 RNA polymerase was expressed in cells with an expanded genetic code and used in the photochemical activation of genes under control of an orthogonal T7 promoter, demonstrating tight spatial and temporal control. The synthetic gene expression system was validated with two reporter genes (luciferase and EGFP) and applied to the light-triggered transcription of short hairpin RNA constructs for the induction of RNA interference.
81 citations
TL;DR: The results show that simultaneous triggering of TRAIL-mediated death receptor pathway and downregulation of Bcl-2 by shRNA leads to enhanced eradication of gliomas and serves as a template in developing and monitoring combination therapies for the treatment of drug-resistant cancers.
81 citations
TL;DR: It is demonstrated that HIF-1&agr; upregulation by double knockdown of PHD and FIH synergistically increases stem cell mobilization and myocardial angiogenesis, leading to improved cardiac function.
Abstract: Background—Under normoxic conditions, hypoxia-inducible factor (HIF)-1α is rapidly degraded by 2 hydroxylases: prolyl hydroxylase (PHD) and factor-inhibiting HIF-1 (FIH). Because HIF-1α mediates the cardioprotective response to ischemic injury, its upregulation may be an effective therapeutic option for ischemic heart failure. Methods and Results—PHD and FIH were cloned from mouse embryonic stem cells. The best candidate short hairpin (sh) sequences for inhibiting PHD isoenzyme 2 and FIH were inserted into novel, nonviral, minicircle vectors. In vitro studies after cell transfection of mouse C2C12 myoblasts, HL-1 atrial myocytes, and c-kit+ cardiac progenitor cells demonstrated higher expression of angiogenesis factors in the double-knockdown group compared with the single-knockdown and short hairpin scramble control groups. To confirm in vitro data, shRNA minicircle vectors were injected intramyocardially after left anterior descending coronary artery ligation in adult FVB mice (n=60). Functional studies...
81 citations