Authors: Wei Ma, Jing Ma, Jie Xu, Chong Qiao, Adam Branscum, Andres Cardenas, Andre T. Baron, Peter Schwartz, Nita J. Maihle and Yingqun Huang

Wei Ma

Department of Obstetrics, Gynecology and Reproductive Sciences; Yale Stem Cell Center; Yale University School of Medicine; New Haven, CT USA; Clinical Department; School of Medicine; Northwest University for Nationalities; Lanzhou, Gansu, P.R. China
These authors contributed equally to this work.

Jing Ma

Department of Obstetrics, Gynecology and Reproductive Sciences; Yale Stem Cell Center; Yale University School of Medicine; New Haven, CT USA; Obstetrics and Gynecology Department; Third Xiangya Hospital of Central South University; Changsha, Hunan, P.R. China
These authors contributed equally to this work.

Jie Xu

Department of Obstetrics, Gynecology and Reproductive Sciences; Yale Stem Cell Center; Yale University School of Medicine; New Haven, CT USA

Chong Qiao

Department of Obstetrics, Gynecology and Reproductive Sciences; Yale Stem Cell Center; Yale University School of Medicine; New Haven, CT USA; Department of Obstetrics and Gynecology; Shengjing Hospital; China Medial University; Shengyang, Liaoning, P.R. China

Adam Branscum

Biostatistics Program; School of Biological and Population Health Sciences; Oregon State University; Corvallis, OR USA

Andres Cardenas

Biostatistics Program; School of Biological and Population Health Sciences; Oregon State University; Corvallis, OR USA

Andre T. Baron

Department of Epidemiology; University of Kentucky; Lexington, KY USA; Department of Obstetrics and Gynecology; Division of Gynecologic Oncology; University of Kentucky; Lexington, KY USA

Peter Schwartz

Department of Obstetrics, Gynecology and Reproductive Sciences; Yale Stem Cell Center; Yale University School of Medicine; New Haven, CT USA

Nita J. Maihle

Department of Obstetrics, Gynecology and Reproductive Sciences; Yale Stem Cell Center; Yale University School of Medicine; New Haven, CT USA; Department of Pathology; Yale University School of Medicine; New Haven, CT USA

Yingqun Huang

Corresponding author: yingqun.huang@yale.edu
Department of Obstetrics, Gynecology and Reproductive Sciences; Yale Stem Cell Center; Yale University School of Medicine; New Haven, CT USA

Abstract:
Emerging evidence suggests that the tumor microenvironment plays a critical role in regulating cancer stem cells (CSCs) and tumor progression through both autocrine and paracrine signaling. Elevated production of bone morphogenetic proteins (BMPs) from human ovarian cancer cells and stroma has been shown to increase CSC proliferation and tumor growth. Here, we report that Lin28, a stem cell factor, binds to BMP4 mRNA in epithelial ovarian carcinoma cells, thereby promoting BMP4 expression at the post-transcriptional level. As co-expression of Lin28 and Oct4 (another stem cell factor) has been implicated in ovarian cancer CSCs, we also determined that high levels of Lin28 are associated with an unfavorable prognosis when co-expressed with high levels of Oct4. Together, these findings uncover a new level of regulation of BMP4 expression and imply a novel Lin28/Oct4/BMP4-mediated mechanism of regulating ovarian tumor cell growth, thus holding potential for the development of new strategies for the diagnosis and treatment of ovarian cancer.

Received: October 2, 2012; Accepted: November 27, 2012; Published Online: December 19, 2012

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