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Silencing expression of UO-44 (CUZD1) using small interfering RNA sensitizes human ovarian cancer cells to cisplatin in vitro

Oncogene volume 26, pages 870–880 (2007)Cite this article

Abstract

Ovarian cancer is currently the second leading cause of gynecological malignancy and cisplatin or cisplatin-based regimens have been the standard of care for the treatment of advance epithelial ovarian cancers. However, the efficacy of cisplatin treatment is often limited by the development of drug resistance either through the inhibition of apoptotic genes or activation of antiapoptotic genes. We have previously reported the overexpression of human UO-44 (HuUO-44) in ovarian cancers and the HuUO-44 antisera markedly inhibited NIH-OVCAR3 ovarian cancer cell attachment and proliferation (Oncogene 23: 5707–5718, 2004). In the present study, we observed through the cancer cell line profiling array that the expression of HuUO-44 was suppressed in the ovarian cancer cell line (SKOV-3) after treatment with several chemotherapeutic drugs. Similarly, this suppression in HuUO-44 expression was also correlated to the cisplatin sensitivity in two other ovarian cancer cell lines NIH-OVCAR3 and OV-90 in a dose-dependent manner. To elucidate the function of HuUO-44 in cisplatin chemoresistance in ovarian cancer cell, small interfering RNAs (siRNAs) were employed to mediate HuUO-44 silencing in ovarian cancer cell line, NIH-OVCAR3. HuUO-44 RNA interference (RNAi) resulted in the inhibition of cell growth and proliferation. Importantly, HuUO-44 RNAi significantly increased sensitivity of NIH-OVCAR3 to cytotoxic stress induced by cisplatin (P<0.01). Strikingly, we have also demonstrated that overexpression of HuUO-44 significantly conferred cisplatin resistance in NIH-OVCAR3 cells (P<0.05). Taken together, UO-44 is involved in conferring cisplatin resistance; the described HuUO-44-specific siRNA oligonucleotides that can potently silence HuUO-44 gene expression may prove to be valuable pretreatment targets for antitumor therapy or other pathological conditions that involves aberrant HuUO-44 expression.

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Acknowledgements

This work was supported by funding from the National Medical Research Council of Singapore under the Grant NMRC/0887/2004 awarded to Huynh Hung.

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Authors and Affiliations

  1. Division of Cellular and Molecular Research, Laboratory of Molecular Endocrinology, National Cancer Centre of Singapore, Singapore, Singapore

    C T C Leong, C K Ong & H Huynh

  2. Department of Pharmacology, National University of Singapore, Singapore, Singapore

    C T C Leong, C K Ong & H Huynh

  3. Department of Obstetrics and Gynaecology, Singapore General Hospital, Singapore, Singapore

    S K Tay

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  1. C T C Leong
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  2. C K Ong
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  4. H Huynh
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Correspondence to H Huynh.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Leong, C., Ong, C., Tay, S. et al. Silencing expression of UO-44 (CUZD1) using small interfering RNA sensitizes human ovarian cancer cells to cisplatin in vitro. Oncogene 26, 870–880 (2007). https://doi.org/10.1038/sj.onc.1209836

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