Double‐stranded Decoy Oligonucleotides as new Biopharmaceuticals

Wagner, Andreas H.; Leyen, Heiko E. von der

doi:10.1002/9783527620982.ch9

Cited by 2 publications

(1 citation statement)

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“…Transcription factor ODNs decoys (TFDs) are short double‐stranded DNA molecules that emerged as a novel class of oligonucleotide‐based drugs. This type of ODNs specifically binds to the specific gene's DNA binding site in a target transcription factor and declines TF activity and the related genes expression (Hecker & Wagner, ; Johari & Zargan, ; Morishita et al, ; Wagner & Von der Leyen, ). In this way, TFDs, preferentially to the other silencing oligonucleotides, which aim only one single mRNA at a target, is designed to inhibit multiple genes involved in the specific pathways at the pretranscription level.…”

Section: Introductionmentioning

confidence: 99%

Suppressing the metastatic properties of the breast cancer cells using STAT3 decoy oligodeoxynucleotides: A promising approach for eradication of cancer cells by differentiation therapy

Rahmati

Johari

Kadivar

et al. 2020

Journal Cellular Physiology

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Due to the presence of cancer stem cells (CSCs), breast cancer often relapsed after conventional therapies. Strategies that induce differentiation of CSCs will be helpful in eradication of tumor cells, so we designed an oligodeoxynucleotide (ODNs) for targeting of signal transducer and activator of transcription 3 (STAT3) transcription factor which is involved in stemness, and constitutively activated in triple‐negative breast cancer. Molecular docking and electrophoretic mobility shift assay analysis showed that decoy ODN bound specifically to the DNA binding site of STAT3 protein. The prevalent uptake of Cy3‐labeled ODNs is in the cytoplasm and the nucleus of MDA‐MB‐231 treated cells. STAT3 decoy ODNs treatment showed cell growth inhibition by decreasing cell viability (17%), increasing the percentage of arrested cells in G0/G1 phases (18%), and triggering apoptosis (29%). Migration and invasion potential decreased from 10.77 to 6.76 µm/hr, by wound closure rate, and migrated/invaded percentage by 26.4% and 15.4% in the transwell assays, respectively. CD44 protein expression level on the cell surface also decreased, while CD24 increased. Mammosphere formation efficiency reduced in terms of tumorsphere size by 47%, while the required time increased. Cells morphology was changed, and lipid droplets were accumulated in the cytoplasm compared to the control and scrambled groups, in all assays (repeated triplicate). Furthermore, the gene expression of all downstream targets significantly decreased owing to suppressing the STAT3 transcription factor. Overall, the results confirmed the antitumor effects of STAT3 decoy in MDA‐MB‐231 cells. Thus, it seems that STAT3 decoy ODNs might be considered as an auxiliary tool for breast cancer eradicating by the differentiation therapy approach.

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Section: Introductionmentioning

confidence: 99%