Induction of Drug Resistance and Transformation in Human Cancer Cells by the Noncoding RNA CUDR

Overview

Journal RNA

Specialty Molecular Biology

Date 2007 Apr 10

PMID 17416635

Citations 61

Authors

Wing Pui Tsang

Timothy W L Wong

Albert H H Cheung

Chloe N N Co

Tim Tak Kwok

Affiliations

Soon will be listed here.

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 drug-induced apoptosis. The full-length CUDR mRNA transcript is approximately 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.

Citing Articles

Competitive endogenous RNA networks: Decoding the role of long non-coding RNAs and circular RNAs in colorectal cancer chemoresistance.

Khalafizadeh A, Hashemizadegan S, Shokri F, Bakhshinejad B, Jabbari K, Motavaf M J Cell Mol Med. 2024; 28(7):e18197.

PMID: 38506091 PMC: 10951891. DOI: 10.1111/jcmm.18197.

Insights into the involvement of long non-coding RNAs in doxorubicin resistance of cancer.

Zhang H, Hu Y, Deng J, Fang G, Zeng Y Front Pharmacol. 2023; 14:1243934.

PMID: 37781691 PMC: 10540237. DOI: 10.3389/fphar.2023.1243934.

HERVs and Cancer-A Comprehensive Review of the Relationship of Human Endogenous Retroviruses and Human Cancers.

Stricker E, Peckham-Gregory E, Scheurer M Biomedicines. 2023; 11(3).

PMID: 36979914 PMC: 10046157. DOI: 10.3390/biomedicines11030936.

Long Non-coding RNA UCA1a Promotes Proliferation via PKM2 in Cervical Cancer.

Yu M, Xue S, Chen X, Wu K, Ju L, Tang J Reprod Sci. 2022; 30(2):601-614.

PMID: 35927414 DOI: 10.1007/s43032-022-01042-6.

Construction of a Metabolism-Related Long Non-Coding RNAs-Based Risk Score Model of Hepatocellular Carcinoma for Prognosis and Personalized Treatment Prediction.

Zhang P, Chen L, Wu S, Ye B, Chen C, Shi L Pathol Oncol Res. 2022; 28:1610066.

PMID: 35685867 PMC: 9171512. DOI: 10.3389/pore.2022.1610066.

References

Yang X, Edgerton S, Thor A . Reconstitution of caspase-3 sensitizes MCF-7 breast cancer cells to radiation therapy. Int J Oncol. 2005; 26(6):1675-80. View

Szakacs G, Paterson J, Ludwig J, Booth-Genthe C, Gottesman M . Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 2006; 5(3):219-34. DOI: 10.1038/nrd1984. View

Jaattela M . Multiple cell death pathways as regulators of tumour initiation and progression. Oncogene. 2004; 23(16):2746-56. DOI: 10.1038/sj.onc.1207513. View

Devarajan E, Sahin A, Chen J, Krishnamurthy R, Aggarwal N, Brun A . Down-regulation of caspase 3 in breast cancer: a possible mechanism for chemoresistance. Oncogene. 2002; 21(57):8843-51. DOI: 10.1038/sj.onc.1206044. View

Fojo T, Bates S . Strategies for reversing drug resistance. Oncogene. 2003; 22(47):7512-23. DOI: 10.1038/sj.onc.1206951. View

Fire A, Xu S, Montgomery M, Kostas S, Driver S, Mello C . Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998; 391(6669):806-11. DOI: 10.1038/35888. View

Yang X, Sladek T, Liu X, Butler B, Froelich C, Thor A . Reconstitution of caspase 3 sensitizes MCF-7 breast cancer cells to doxorubicin- and etoposide-induced apoptosis. Cancer Res. 2001; 61(1):348-54. View

Montgomery M, Xu S, Fire A . RNA as a target of double-stranded RNA-mediated genetic interference in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1998; 95(26):15502-7. PMC: 28072. DOI: 10.1073/pnas.95.26.15502. View

Wang X, Zhang Z, Wang H, Cai J, Xu Q, Li M . Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clin Cancer Res. 2006; 12(16):4851-8. DOI: 10.1158/1078-0432.CCR-06-0134. View

10.

Hurst L, Smith N . Molecular evolutionary evidence that H19 mRNA is functional. Trends Genet. 1999; 15(4):134-5. DOI: 10.1016/s0168-9525(99)01696-0. View

11.

Cole S, Deeley R . Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP. Bioessays. 1999; 20(11):931-40. DOI: 10.1002/(SICI)1521-1878(199811)20:11<931::AID-BIES8>3.0.CO;2-J. View

12.

Lage H, Helmbach H, Dietel M, Schadendorf D . Modulation of DNA topoisomerase II activity and expression in melanoma cells with acquired drug resistance. Br J Cancer. 2000; 82(2):488-91. PMC: 2363299. DOI: 10.1054/bjoc.1999.0947. View

13.

Winter R, Kramer A, Borkowski A, Kyprianou N . Loss of caspase-1 and caspase-3 protein expression in human prostate cancer. Cancer Res. 2001; 61(3):1227-32. View

14.

Kwok T, Sutherland R . Epidermal growth factor reduces resistance to doxorubicin. Int J Cancer. 1991; 49(1):73-6. DOI: 10.1002/ijc.2910490114. View

15.

Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S . Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature. 2002; 420(6915):563-73. DOI: 10.1038/nature01266. View

16.

Lindbo J, Silva-Rosales L, Proebsting W, Dougherty W . Induction of a Highly Specific Antiviral State in Transgenic Plants: Implications for Regulation of Gene Expression and Virus Resistance. Plant Cell. 1993; 5(12):1749-1759. PMC: 160401. DOI: 10.1105/tpc.5.12.1749. View

17.

Eddy S . Non-coding RNA genes and the modern RNA world. Nat Rev Genet. 2001; 2(12):919-29. DOI: 10.1038/35103511. View

18.

Erdmann V, Barciszewska M, Hochberg A, De Groot N, Barciszewski J . Regulatory RNAs. Cell Mol Life Sci. 2001; 58(7):960-77. PMC: 11337372. DOI: 10.1007/PL00000913. View

19.

Fong P, Xue W, Ngan H, Chiu P, Chan K, Tsao S . Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study. J Clin Pathol. 2006; 59(2):179-83. PMC: 1860314. DOI: 10.1136/jcp.2005.028027. View

20.

Miyashiro K, Beckel-Mitchener A, Purk T, Becker K, Barret T, Liu L . RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron. 2003; 37(3):417-31. DOI: 10.1016/s0896-6273(03)00034-5. View