Induction of drug resistance and transformation in human cancer cells by the noncoding RNA CUDR
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AbstractRefractory 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, cancer up-regulated drug resistant (CUDR) 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 CUDR mRNA transcript is similar to 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 CUDR cDNA sequence, and no recombinant protein was detected from in vitro translation or from a protein lysate of human cancer cells after CUDR transfection. Therefore, CUDR is likely to exert its function as a noncoding RNA. Stable transfection with the CUDR 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 CUDR transfectants. On the other hand, overexpression of CUDR promoted anchorage-independent growth in A431 cells. Results from the present study suggest that CUDR may likely regulate the drug sensitivity and promote cellular transformation at least through caspase 3-dependent apoptosis.
All Author(s) ListTsang WP, Wong TWL, Cheung AHH, Co CNN, Kwok TT
Journal nameRNA
Year2007
Month6
Day1
Volume Number13
Issue Number6
PublisherCOLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Pages890 - 898
ISSN1355-8382
LanguagesEnglish-United Kingdom
Keywordscaspase 3; cellular transformation; CUDR; drug resistance; ncRNA
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY

Last updated on 2021-15-02 at 02:07