Induction of drug resistance and transformation in human cancer cells by the noncoding RNA CUDR

Abstract

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, 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 druginduced apoptosis. The full-length CUDR 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 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.

Expression of Noncoding Vault RNA in Human Malignant Cells and Its Importance in Mitoxantrone Resistance

“…We have also found that in other known proteins such as BCRP and MVP, which are known to render the cellular resistance to mitoxantrone, expressions could not be correlated for their role in mitoxantrone resistance in our studies. Recently, two noncoding RNAs (miR-221/222 and CUDR) have also been shown to play an important role in mediating drug resistance in cancer cells (25,26). In summary, this study has identified another noncoding RNA (vRNA-1) that plays an important role by mediating the drug-resistant phenotype of malignant cells.…”

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

“…92,93 Cancer upregulated drug resistant (CUDR) is an lncRNA that exhibits elevated expression in multiple cancers, including CRC. 94,95 Tsang et al 94 provided evidence that increasing CUDR gene levels in vitro in human squamous carcinoma cells resulted in increased resistance to doxorubicin and etoposide and decreased levels of drug-induced apoptosis via the downregulation of caspase-3. The question of whether similar mechanisms operate in CRC should be examined further, but this observation suggests that lncRNA manipulation-based gene therapy may be beneficial in overcoming drug resistance and in designing personalized therapeutics for cancer patients.…”

Long non-coding RNA UCA1a(CUDR) promotes proliferation and tumorigenesis of bladder cancer

“…In addition, there was evidence to suggest that CUDR was only expressed in human placenta but not in other normal tissues; CUDR was upregulated in human colon, cervix, and lung cancer (10). These results guided us to investigate the role of UCA1a(CUDR) in embryonic development and bladder cancer progression.…”

“…Interestingly, sequence comparison of the UCA1 and UCA1a(CUDR) cDNA revealed a 1,265 bp common region. CUDR was believed to exert its function as an lncRNA in the regulation of drug resistance and cellular transformation (10). In addition, CUDR was upregulated in various tumor tissues, including colon, cervix, and lung cancer (10).…”

“…CUDR was believed to exert its function as an lncRNA in the regulation of drug resistance and cellular transformation (10). In addition, CUDR was upregulated in various tumor tissues, including colon, cervix, and lung cancer (10). However, the role of UCA1a(CUDR) in bladder cancer has not yet been reported.…”