Abstract
Lin28 and Oct4 are highly expressed in human embryonic stem (ES) cells and, along with two other stem cell marker proteins (Nanog and Sox2), together can convert human somatic cells to pluripotency. As an RNA-binding protein, Lin28 acts to stimulate the translation of a specific subset of mRNAs, and to inhibit the biogenesis of a group of microRNAs. Oct4 is a transcription factor essential for the maintenance of pluripotency and survival of ES cells. In this study, we report that a sub-population of epithelial ovarian cancer (EOC) cells co-expresses Lin28 and Oct4 as demonstrated in the analyses of both cell lines and patient tumor samples. We also observe that the combined expression of these proteins in tumor samples is correlated with advanced tumor grade. Intriguingly, when the expression of these two proteins is repressed in the same cells using RNA interference, there is significant reduction in cell growth and survival. We thus propose that Lin28 and Oct4 may have important roles in the initiation and/or progression of EOC, and consequently may serve as important molecular diagnostics and/or therapeutic targets for the development of novel treatment strategies in EOC patients.
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Acknowledgements
We thank Jianyu Jin for technical assistance, Jill Reiter for extracts from ovarian cancer cells and insightful scientific discussions, Philip Low and Gil Mor for cell lines and Jason Wilken for critical discussions and reading of this paper. This study was supported by the Fannie E Rippel Foundation and a CT Stem Cell Grant 09SCAYALE14 to YH, and a Yale School of Medicine ‘Senior Women in Medicine’ Professorship, and NIH CA 79808 to NJM.
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Peng, S., Maihle, N. & Huang, Y. Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer. Oncogene 29, 2153–2159 (2010). https://doi.org/10.1038/onc.2009.500
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DOI: https://doi.org/10.1038/onc.2009.500