Lin28 regulates BMP4 and functions with Oct4 to affect ovarian tumor microenvironment

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

doi:10.4161/cc.23028

Lin28 regulates BMP4 and functions with Oct4 to affect ovarian tumor microenvironment

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

Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

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.

Original language	English (US)
Pages (from-to)	88-97
Number of pages	10
Journal	Cell Cycle
Volume	12
Issue number	1
DOIs	https://doi.org/10.4161/cc.23028
State	Published - Jan 1 2013

Keywords

BMP4
Lin28/Oct4
Ovarian cancer
Posttranscriptional
Tumor microenvironment

ASJC Scopus subject areas

Molecular Biology
Developmental Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.4161/cc.23028

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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.",

keywords = "BMP4, Lin28/Oct4, Ovarian cancer, Posttranscriptional, Tumor microenvironment",

author = "Wei Ma and Jing Ma and Jie Xu and Chong Qiao and Adam Branscum and Andres Cardenas and Baron, {Andre T.} and Peter Schwartz and Maihle, {Nita J.} and Yingqun Huang",

note = "Funding Information: We would like to thank David Rimm for sharing expertise, reagents and analytic tools related to AQUA, Setsuko Chambers and Wenxin Zheng for their development of the TMA used in these studies, and Richard Hochberg and Lingeng Lu for critical reading of the manuscript. 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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AU - Ma, Wei

AU - Ma, Jing

AU - Xu, Jie

AU - Qiao, Chong

AU - Branscum, Adam

AU - Cardenas, Andres

AU - Baron, Andre T.

AU - Schwartz, Peter

AU - Maihle, Nita J.

AU - Huang, Yingqun

N1 - Funding Information: We would like to thank David Rimm for sharing expertise, reagents and analytic tools related to AQUA, Setsuko Chambers and Wenxin Zheng for their development of the TMA used in these studies, and Richard Hochberg and Lingeng Lu for critical reading of the manuscript. 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.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

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KW - Lin28/Oct4

KW - Ovarian cancer

KW - Posttranscriptional

KW - Tumor microenvironment

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Lin28 regulates BMP4 and functions with Oct4 to affect ovarian tumor microenvironment

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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