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.
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…]
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…]
- Third collaboration to investigate the potential application of Silence’s proprietary RNAi delivery technologies in the development of novel microRNA-based therapeutics
Silence Therapeutics plc (AIM: SLN) (“Silence”), a leading RNA interference (RNAi) therapeutics company, announces that it has signed an agreement with miRagen Therapeutics, Inc. (“miRagen”), to assess the delivery potential of Silence’s proprietary DBTC delivery system with miRagen’s novel microRNA- (miRNA-) based therapeutics. MiRagen is a pre-clinical stage biopharmaceutical company founded to develop innovative miRNA-based therapeutics for the treatment of cardiovascular and muscle disease.
Under the terms of the agreement, miRagen will provide Silence with specific miRNA sequences, which Silence will formulate with its proprietary DBTC delivery system in order to develop multiple candidate drugs. MiRagen will undertake in vitro and in vivo studies of the candidate drugs developed under the agreement and select lead candidates for further evaluation. Financial terms of the collaboration are not disclosed.
DBTC is a proprietary RNAi delivery system developed by Silence. It is a novel lipid-based formulation that functionally delivers short interfering RNA (siRNA) to liver endothelial cells, hepatocytes and other liver cell types with high efficiency.
Thomas Christely, Chief Executive Officer of Silence Therapeutics, said: “We are delighted to be collaborating with miRagen. This is the third collaboration that [click to continue…]
This is an amazing video animation from Nature Reviews Genetics!
This animation introduces the principles of RNAi involving small interfering RNAs (siRNAs) and microRNAs (miRNAs). It takes you on an audio-visual journey through the steps of gene expression and shows you an up-to-date view of how RNAi can silence specific mRNAs in the cytoplasm.
There is an accompanying slideshow which provides further information about RNAi and small RNAs.
Stabilization of hepatitis C virus RNA by an Ago2–miR-122 complex MicroRNAs regulate eukaryotic gene expression by binding to regions of imperfect complementarity in mRNAs, typically in the 3′ UTR, recruiting an Argonaute (Ago) protein complex that usually results in translational repression or destabilization of the target RNA. The translation and decay of mRNAs are closely [...]
-Regulus, Accelerate Brain Cancer Cure (ABC2) and Samsung Medical Center to Advance microRNA Therapeutics for Glioblastoma – LA JOLLA, Calif., Dec. 12, 2011 /PRNewswire/ – Regulus Therapeutics Inc., a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today announced the initiation of a new discovery effort in microRNA therapeutics for the treatment [...]
Proprietary microRNA Diagnostic for Identification of Cancer of Unknown Primary Now Available in All 50 U.S. States PHILADELPHIA, PA and REHOVOT, ISRAEL–(Marketwire – Dec 9, 2011) – Rosetta Genomics, Ltd. (NASDAQ: ROSG), a leading developer and provider of microRNA-based molecular diagnostics, announced that the New York State Department of Health has approved miRview® mets² for [...]
Despite accumulating data on animal and plant microRNAs and their functions, existing public miRNA resources usually collect miRNAs from a very limited number of species. A lot of microRNAs, including those from model organisms, remain undiscovered. As a result there is a continuous need to search for new microRNAs. Izabela Makałowska’s Laboratory of Evolutionary Genomics [...]
How the human brain and human cognitive abilities evolved in less than six million years has long puzzled scientists. A new study conducted by scientists in China and Germany, and published December 6 in the online, open-access journal PLoS Biology, now provides a possible explanation by showing that activity levels of genes in the human [...]
miRecords
Manually curated database of experimentally validated miRNA–target interactions
miRvar
Database for Genomic Variations in microRNAs
PMRD: plant microRNA database
This database includes all publicly known plant miRNA sequences – including those in miRBase.
psRNATarget
A Plant Small RNA Target Analysis Server
TargetScan
TargetScanS predicts biological targets of miRNAs by searching for the presence of conserved 8mer and 7mer sites that match the seed region of each miRNA.