title: Lin28 regulates BMP4 and functions with Oct4 to affect ovarian tumor microenvironment.
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.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Ma
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Chong
authors.initials: C
authors.lastname: Qiao
authors.forename: Adam
authors.initials: A
authors.lastname: Branscum
authors.forename: Andres
authors.initials: A
authors.lastname: Cardenas
authors.forename: Andre T
authors.initials: AT
authors.lastname: Baron
authors.forename: Peter
authors.initials: P
authors.lastname: Schwartz
authors.forename: Nita J
authors.initials: NJ
authors.lastname: Maihle
authors.forename: Yingqun
authors.initials: Y
authors.lastname: Huang
mesh_terms: D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D055415:Bone Morphogenetic Protein 4; C000715187:Lin28A protein, human; D050814:Octamer Transcription Factor-3; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins