Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer.
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.
Peng
S
S
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510, USA.
Maihle
N J
NJ
Huang
Y
Y
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D018450:Disease Progression; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology*
C000715187:Lin28A protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016601:RNA-Binding Proteins