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Lin28 Regulates BMP4 and Functions with Oct4 to Affect Ovarian Tumor Microenvironment

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https://ir.library.oregonstate.edu/concern/articles/k06988306

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  • 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 posttranscriptional 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.
  • This is the author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Landes Bioscience and can be found at: http://www.landesbioscience.com/journals/cc/.
  • Keywords: Ovarian cancer, Posttranscriptional, BMP4, Tumor microenvironment, Lin28/Oct4
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  • Ma, W., Ma, J., Xu, J., Qiao, C., Branscum, A., Cardenas, A., & Huang, Y. (2013, January 1). Lin28 regulates BMP4 and functions with Oct4 to affect ovarian tumor microenvironment. Cell Cycle, 12(1), 88-97. doi:10.4161/cc.23028
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  • 12
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  • 1
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  • This work was supported by a 09SCAYALE14 Connecticut Stem Cell Grant and a 1063338 Albert McKern Scholar Award to Y.H., and a Yale School of Medicine ‘Senior Women in Medicine’ Professorship to N.J.M.
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