Selective Anti-Gene Therapy for Cancer: Principles and Prospects.

Cohen, Jack S.

doi:10.1620/tjem.168.351

Cited by 6 publications

(2 citation statements)

References 9 publications

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“…3 Most asDNAs and ODNs activate RNases H, which cleave and degrade the RNA of DNA-RNA hybrids (15,20,52,53). AsDNA can also block translation by steric hindrance of the ribosomes (14,54,55), and miRs primarily inhibit translation of proteins (13,56). ODN-Raf as well as miR-125b did not lead to a reduction of c-raf-1 mRNA but reduced C-Raf protein levels by 50% (Figs.…”

Section: Discussionmentioning

confidence: 96%

“…SiRNA and asDNA primarily lead to reduction of mRNA by cleavage, whereas miRs primarily block translation (11)(12)(13). Inhibition of translation has also been described for asDNA as secondary effect (14,15). ODNs are a special class of short hairpin-looped DNAs that can induce cleavage of viral RNAs via a retroviral or cellular RNase H and therefore are active as antiviral agents (16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

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A Short Hairpin DNA Analogous to miR-125b Inhibits C-Raf Expression, Proliferation, and Survival of Breast Cancer Cells

Hofmann

Heinrich

Radziwil

et al. 2009

Molecular Cancer Research

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The noncoding RNA miR-125b has been described to reduce ErbB2 protein expression as well as proliferation and migration of cancer cell lines. As additional target of miR-125b, we identified the c-raf-1 mRNA by sequence analysis. We designed a short hairpin-looped oligodeoxynucleotide (ODN) targeted to the same 3′ untranslated region of c-raf-1 mRNA as miR-125b. The fully complementary ODN antisense strand is linked to a second strand constituting a partially double-stranded structure of the ODN. Transfection of the c-raf-1-specific ODN (ODN-Raf) in a breast cancer cell line reduced the protein levels of C-Raf, ErbB2, and their downstream effector cyclin D1 similar to miR-125b. MiR-125b as well as ODN-Raf showed no effect on the c-raf-1 mRNA level in contrast to small interfering RNA. Unlike miR-125b, ODN-Raf induced a cytopathic effect. This may be explained by the structural properties of ODN-Raf, which can form G-tetrads. Thus, the short hairpin-looped ODN-Raf, targeting the same region of c-raf-1 as miR-125b, is a multifunctional molecule reducing the expression of oncoproteins and stimulating cell death. Both features may be useful to interfere with tumor growth. (Mol Cancer Res 2009;7(10):1635-44)

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