Low-Level Expression of miR-375 Correlates with Poor Outcome and Metastasis While Altering the Invasive Properties of Head and Neck Squamous Cell Carcinomas.
Researchers at Department of Pathology, Albert Einstein College of Medicine used global miRNA expression profiling of head and neck squamous cell carcinoma (HNSCC) samples and adjacent normal tissue to rank those miRNAs that were most significantly altered in a patient population of 123. Harris et al. evaluated 736 of the currently known 1898 unique mature human microRNAs. Rank Consistency Score analysis revealed miR-375 to have the most significantly lowered miRNA levels in tumors relative to matched adjacent nonmalignant tissue from the same patient.
While this result has been previously observed by other groups, this latest study reveals that low miR-375 expression levels correlate significantly with cancer survival and distant metastasis. In a study of 123 primary HNSCC patients using multivariable Cox proportional hazard ratios (HR) and 95% confidence intervals (CI), both death from disease (HR: 12.8, 95% CI: 3 to 49) and incidence of distant metastasis (HR: 8.7, 95% CI: 2 to 31) correlated with lower expression levels of miR-375 regardless of the site or stage of the tumor. In addition, oral cavity tumor cell lines (eg, UMSCC1 and UMSCC47) overexpressing miR-375 were significantly less invasive in vitro than their matched empty vector controls.
The authors conclude that miR-375 may be suitable as a potential prognostic marker of poor outcome and metastasis in HNSCC and that it may function by suppressing the tumor’s invasive properties.
Harris T, Jimenez L, Kawachi N, Fan JB, Chen J, Belbin T, Ramnauth A, Loudig O, Keller CE, Smith R, Prystowsky MB, Schlecht NF, Segall JE, Childs G.
Low-Level Expression of miR-375 Correlates with Poor Outcome and Metastasis While Altering the Invasive Properties of Head and Neck Squamous Cell Carcinomas.
Am J Pathol., in press.
http://www.sciencedirect.com/science/article/pii/S0002944011010947
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Single nucleotide polymorphisms (SNPs) can lead to the susceptibility and onset of diseases through their effects on gene expression at the posttranscriptional level. Recent findings indicate that SNPs could create, destroy, or modify the efficiency of miRNA binding to the 3′UTR of a gene, resulting in gene dysregulation. With the rapidly growing number of published disease-associated SNPs (dSNPs), there is a strong need for resources specifically recording dSNPs on the 3′UTRs and their nucleotide distance from miRNA target sites. Bruno et al. from the Center for Computational Research SUNY at the University of Buffalo presents miRdSNP, a database incorporating three important areas of dSNPs, miRNA target sites, and diseases.
miRdSNP provides a unique database of dSNPs on the 3′UTRs of human genes manually curated from PubMed. The current release includes 786 dSNP-disease associations for 630 unique dSNPs and 204 disease types. miRdSNP annotates genes with experimentally confirmed targeting by miRNAs and indexes miRNA target sites predicted by TargetScan and PicTar as well as potential miRNA target sites newly generated by dSNPs. A robust web interface and search tools are provided for [click to continue…]
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Patent Protects Use of UNAs in Multiple Nucleic Acid Constructs Including siRNAs, microRNA Mimics, Antagomirs and Single-Stranded Constructs
BOTHELL, WA–(Marketwire – Jan 23, 2012) – Marina Biotech, Inc. (NASDAQ: MRNAD), a leading oligonucleotide-based drug discovery and development company today announced that the Intellectual Property Office of New Zealand (IPONZ) has issued a Notice of Acceptance for patent application 580712. The claims broadly cover multiple sequence independent and length independent, nucleic acid constructs having one or more unlocked nucleobase analogs (UNAs). The nucleic acid constructs of the patent include both RISC and dicer length siRNAs, both microRNA mimetics and microRNA antagomirs as well as single-stranded oligonucleotides.
“The company continues to deliver on a patent strategy which expands and protects our broad oligonucleotide therapeutics platform,” stated J. Michael French, President and CEO at Marina Biotech. “This allowed patent is part of our global UNA patent portfolio providing broad and comprehensive protection for multiple, distinct UNA containing nucleic acid constructs all of which can modulate gene expression through distinct cellular mechanisms including RNAi, mRNA translational inhibition, steric blocking or microRNA pathways. This patent allowance reinforces our belief that we will continue to obtain patent protection for our UNA technology in other countries thereby strengthening the company’s intellectual property position for our broad oligonucleotide drug discovery platform.”
UNA are non-nucleotide, acyclic monomers which provide greater structural flexibility in a nucleic acid strand. Their value has been demonstrated in Marina Biotech’s proprietary UsiRNA constructs which are double-stranded small interfering RNA (siRNA) incorporating at least one UNA monomer and are distinct from the standard siRNA constructs used by others in the industry. UsiRNAs are specifically designed to provide greater specificity for RNAi-based therapeutics. Substitution with UNA [click to continue…]
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- The experiment tested a specific microRNA gene that was identified in
corn and soybean, and confirmed the potential to develop plants capable
of withstanding intermittent irrigation with seawater and growth in high
salinity soils - During the experiment, plants were intermittently irrigated with salt
water with three times the salinity level of seawater - Rosetta Green has previously demonstrated that microRNA genes are
capable of improving plants under extreme drought conditions
REHOVOT, Israel, Jan. 10, 2012 (GLOBE NEWSWIRE) — The Israeli agro-biotechnology company Rosetta Green, which develops improved crops for the agriculture industry, reports successful experimental results in which plants were grown using seawater irrigation. The experiment was conducted on tobacco plants which are used as model plants for corn and soybean. The plants that were improved by a microRNA gene were found to have an enormous potential to grow under irrigation with seawater.
In the said experiment, which took place in recent months in Rosetta Green’s controlled and unique growth rooms in Rehovot, the effect of the microRNA gene was tested on tobacco plants under conditions of seawater irrigation. For that purpose, plants that were improved by this microRNA gene and control plants that did not undergo such improvement were irrigated with salt water with triple the salinity level of seawater. Subsequently, both plant groups were put back [click to continue…]
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