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MicroRNA Family Link in Tumor-Suppressor Network


Two groups of researchers separately published data showing that the p53 tumor-suppressor gene directly targets members of the evolutionarily conserved miR-34 family of microRNAs, which is known to suppress cell proliferation.

The findings, which appeared in the online editions of Nature and Molecular Cell, suggest that this small non-coding RNA family may be a key component in the p53 tumor-suppressor network, which controls cellular responses to signals such as DNA damage and oncogene activation.

In the Nature paper, researchers from Cold Spring Harbor Laboratory, Rosetta Inpharmatics, and Applied Biosystems describe how three members of the miR-34 family are seemingly employed by p53.

“A global decrease in … miRNA levels is often observed in human cancers, indicating that small RNAs may have an intrinsic function in tumor suppression,” the paper’s authors wrote. To identify miRNA components of tumor-suppressor pathways, they examined miRNA expression profiles in both normal and p53-deficient mouse embryonic fibroblasts.

Meanwhile, in Molecular Cell, investigators from Johns Hopkins University School of Medicine reported that miR-34a appears to modulate and fine-tune the gene-expression program triggered by p53.

After conducting global miRNA expression analyses in p53 wild-type colon cancer cells and an isogenic cell line in which both alleles of p53 were inactivated, the researchers identified miR-34a as the miRNA exhibiting the greatest level of expression change when the cells were treated with a DNA-damaging drug known to induce p53.

The team transiently transfected miR-34a into the wild-type and p53-deficient colon cancer cells, then measured apoptotic cell death.

“These data suggest that miR-34a participates in the apoptotic program triggered by p53 activation,” the authors wrote.
Doug Macron

Short Reads

A Columbia University Medical Center CLIA-certified lab agreed to validate Rosetta Genomics’ microRNA-based Cancer of Unknown Primary diagnostic tool. The CUP diagnostic is designed to help clinicians identify the origin of metastatic tumors.

eXegenics is purchasing Ophthalmic Technologies, a privately held company that markets ophthalmic diagnostics and imaging equipment. eXegenics recently bought Acuity Pharmaceuticals.

Kreatech Biotechnology introduced a low-input microRNA isolation and labeling kit, containing reagents to isolate miRNA from tissue or cultured cells and reagents to label those samples for microarray analysis. Another version, with ULS labeling molecule bound to Cy3 and Cy5 dyes, is available from GE Healthcare.

The National Science Foundation issued phase I Small Business Innovation Research grants to two companies to use RNAi-based technologies to overcome key agricultural hurdles: parasites and disease. One grant, for $100,000, was given to Divergence to create crops resistant to parasitic nematodes. The other, for $97,415, was awarded to AviGenics to develop transgenic poultry resistant to avian influenza.
Faqing Huang at the University of Southern Mississippi won a two-year grant from the National Cancer Institute, worth $164,250 in its first year, to develop a folate receptor-mediated delivery technique for siRNAs.


US patent application 20070081982. Multiple RNAi expression cassettes for simultaneous delivery of RNAi agents related to heterozygotic expression patterns. Inventors: Elisabeth Evertsz and Sarah Brashears. Filed: April 28, 2006.
The abstract says, “The present invention provides compositions and methods suitable for expressing y-x multiple-RNAi agents against an allele or alleles of interest in cells, tissues or organs of interest in vitro and in vivo so as to treat diseases.”  This affects “gene expression of one or more genes in a subject or cell culture [by applying] a genetic construct comprising at least one ddRNAi expression cassette.”

US patent application 20070082864. Method for inducing a specific RNAi activity in cells and nucleic acids for carrying out said method. Inventors: Annick Harel-Bellan, Slimane Ait-Si-Ali, and Monsef Benkirane. Filed: October 19, 2004.
The patent describes “a method for inducing activity of a specific RNAi into eukaryote cells in which the TAT protein and a nucleic acid coding for a nucleotide sequence comprising the sense and antisense sequences of an RNAi of interest are introduced.”

Data Point


BioSurfaces was awarded a one-year grant from National Science Foundation worth about $150,000. This grant will be used to create a material for stents and grafts that is fibrous and can allow small interfering RNAs and viral vectors through.

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