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Induction of drug resistance and transformation in human cancer cells by the noncoding RNA CUDR |
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Abstract10.1261/rna.359007 Refractory to apoptosis induced by anticancer drugs is one of the major causes of drug resistance in human cancers. The involvement of noncoding RNA (ncRNA) in cancer cell drug resistance has not yet been reported. By using the technique of RT-PCR-based differential display, a novel gene, gene, was found to be overexpressed in a doxorubicin-resistant subline of human squamous carcinoma A431 and A10A cells, which were also more resistant to drug-induced apoptosis. The full-length mRNA transcript is ∼2.2 kb as detected by Northern blot analysis and has no sequence homology with other genes identified so far. Interestingly, no distinct open reading frame was found throughout the cDNA sequence, and no recombinant protein was detected from in vitro translation or from a protein lysate of human cancer cells after transfection. Therefore, is likely to exert its function as a noncoding RNA. Stable transfection with the gene was found to induce resistance to doxorubicin and etoposide as well as drug-induced apoptosis in A431 cells. By Western blot analysis, down-regulations of caspase 3 were observed in transfectants. On the other hand, overexpression of promoted anchorage-independent growth in A431 cells. Results from the present study suggest that may likely regulate the drug sensitivity and promote cellular transformation at least through caspase 3-dependent apoptosis.
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