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Futami K.,GeneCare Research Institute Co. | Furuichi Y.,GeneCare Research Institute Co.
Frontiers in Genetics | Year: 2014

RECQL1 and WRN helicases in the human RecQ helicase family participate maintaining genome stability, DNA repair, replication and recombination pathways in the cell cycle. They are expressed highly in rapidly proliferating cells tumor cells, suggesting that they have important roles in the replication of a genome. Although mice deficient in these helicases are indistinguishable from wild-type mice, their embryonic fibroblasts are sensitive to DNA damage. In tumor cells, silencing the expression of RECQL1 or WRN helicase by RNA interference induces mitotic catastrophe that eventually kills tumor cells at the mitosis stage of cell cycle. By contrast, the same gene-silencing by cognate small RNA (siRNA) never kills normal cells, although cell growth is slightly delayed. These findings indicate that RECQL1 and WRN helicases are ideal molecular targets for cancer therapy. The molecular mechanisms underlying these events has been studied extensively, which may help development of anticancer drugs free from adverse effects by targeting DNA repair helicases RECQL1 and WRN. As expected, the anticancer activity of conventional genotoxic drugs is significantly augmented by combined treatment with RECQL1- or WRN-siRNAs that prevents DNA repair in cancer cells. In this review, we focus on studies that clarified the mechanisms that lead to the specific killing of cancer cells and introduce efforts to develop anticancer RecQ-siRNA drugs free from adverse effects. © 2014 Furuichi and Futami.


The present inventors discovered that inhibition of the expression of various genes associated with chromosome stabilization induces cancer cell-specific apoptosis and inhibits cell proliferation. Compounds that inhibit expression of a gene associated with chromosome stabilization or inhibit the function of a protein encoded by such a gene are thought to have cancer cell-specific apoptosis-inducing effects.


The present inventors discovered that inhibition of the expression of various genes associated with chromosome stabilization induces cancer cell-specific apoptosis and inhibits cell proliferation. Compounds that inhibit expression of a gene associated with chromosome stabilization or inhibit the function of a protein encoded by such a gene are thought to have cancer cell-specific apoptosis-inducing effects.


The present inventors discovered that inhibition of the expression of various genes associated with chromosome stabilization induces cancer cell-specific apoptosis and inhibits cell proliferation. Compounds that inhibit expression of a gene associated with chromosome stabilization or inhibit the function of a protein encoded by such a gene are thought to have cancer cell-specific apoptosis-inducing effects.


Patent
Genecare Research Institute Co. | Date: 2012-11-07

The present inventors discovered that although suppressing expression of the RecQ1 gene, a RecQ helicase family gene, shows suppressive effects on cell proliferation in cancer cells, such effects are not observed in human TIG3 cells (a normal diploid fibroblast cell line), which are normal cells. Hence, the present inventors discovered that siRNAs against RecQ1 gene have cancer cell-specific cell proliferation-suppressing effects that are mediated by suppression of the expression of said gene.


Patent
Genecare Research Institute Co. | Date: 2014-02-26

The present inventors discovered that although suppressing expression of the RecQ1 gene, a RecQ helicase family gene, shows suppressive effects on cell proliferation in cancer cells, such effects are not observed in human TIG3 cells (a normal diploid fibroblast cell line), which are normal cells. Hence, the present inventors discovered that siRNAs against RecQ1 gene have cancer cell-specific cell proliferation-suppressing effects that are mediated by suppression of the expression of said gene.


Patent
Genecare Research Institute Co. | Date: 2012-09-27

The present invention revealed that by suppressing the expression of the WRN gene, the BLM gene, or the RecQ1 gene, which belong to the RecQ helicase family, apoptosis is induced in various cancer cells and their proliferation is suppressed. Compounds that suppress the expression of RecQ helicase family genes or the functions of RecQ helicase proteins are thought to have the activity of inducing apoptosis.


The present inventors discovered that inhibition of the expression of various genes associated with chromosome stabilization induces cancer cell-specific apoptosis and inhibits cell proliferation. Compounds that inhibit expression of a gene associated with chromosome stabilization or inhibit the function of a protein encoded by such a gene are thought to have cancer cell-specific apoptosis-inducing effects.


Patent
Genecare Research Institute Co. | Date: 2010-11-17

PolydG is added to the terminal overhangs of an siRNA. Next, a primer containing a polydC sequence added with a tag sequence is annealed and cDNA is synthesized by a reverse transcription reaction. Quantitative PCR is performed between a primer carrying the same sequence as the tag sequence, and a primer containing the same sequence as the siRNA sequence to be detected. The amount of siRNA of interest can be determined from a calibration curve produced using knows amounts of short-chain dsDNA.


The present inventors discovered that inhibition of the expression of various genes associated with chromosome stabilization induces cancer cell-specific apoptosis and inhibits cell proliferation. Compounds that inhibit expression of a gene associated with chromosome stabilization or inhibit the function of a protein encoded by such a gene are thought to have cancer cell-specific apoptosis-inducing effects.

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