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Leukemia inhibitory factor promotes EMT through STAT3-dependent miR-21 induction

Leukemia inhibitory factor (LIF) is a multi-function cytokine. Its role in cancer is not well-understood. Recent studies including ours show that LIF is frequently overexpressed in many types of human tumors and promotes the progression and metastasis of tumors. However, the underlying mechanism of...

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Autores principales: Yue, Xuetian, Zhao, Yuhan, Zhang, Cen, Li, Jun, Liu, Zhen, Liu, Juan, Hu, Wenwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826169/
https://www.ncbi.nlm.nih.gov/pubmed/26716902
http://dx.doi.org/10.18632/oncotarget.6756
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author Yue, Xuetian
Zhao, Yuhan
Zhang, Cen
Li, Jun
Liu, Zhen
Liu, Juan
Hu, Wenwei
author_facet Yue, Xuetian
Zhao, Yuhan
Zhang, Cen
Li, Jun
Liu, Zhen
Liu, Juan
Hu, Wenwei
author_sort Yue, Xuetian
collection PubMed
description Leukemia inhibitory factor (LIF) is a multi-function cytokine. Its role in cancer is not well-understood. Recent studies including ours show that LIF is frequently overexpressed in many types of human tumors and promotes the progression and metastasis of tumors. However, the underlying mechanism of LIF's promoting effects on tumor progression and metastasis is poorly defined. Epithelial-mesenchymal transition (EMT) plays an important role in tumor metastasis. This study reports that LIF promotes EMT in human tumor cells. Overexpression of LIF promotes tumor cells to acquire mesenchymal features, including morphological changes of cells from epithelial-like to mesenchymal-like, increased expression levels of mesenchymal markers and decreased expression of epithelial markers. Knockdown of endogenous LIF reverses EMT in cancer cells. We further identified that LIF induces the expression of microRNA-21 (miR-21), which in turn mediates the promoting effect of LIF on EMT. LIF induces miR-21 expression through the activation of STAT3. Importantly, blocking miR-21 function greatly abolished the promoting effect of LIF on EMT and the migration ability of cancer cells. Taken together, results from this study identified an important function and a novel underlying mechanism of LIF in EMT and tumor metastasis.
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spelling pubmed-48261692016-05-09 Leukemia inhibitory factor promotes EMT through STAT3-dependent miR-21 induction Yue, Xuetian Zhao, Yuhan Zhang, Cen Li, Jun Liu, Zhen Liu, Juan Hu, Wenwei Oncotarget Research Paper Leukemia inhibitory factor (LIF) is a multi-function cytokine. Its role in cancer is not well-understood. Recent studies including ours show that LIF is frequently overexpressed in many types of human tumors and promotes the progression and metastasis of tumors. However, the underlying mechanism of LIF's promoting effects on tumor progression and metastasis is poorly defined. Epithelial-mesenchymal transition (EMT) plays an important role in tumor metastasis. This study reports that LIF promotes EMT in human tumor cells. Overexpression of LIF promotes tumor cells to acquire mesenchymal features, including morphological changes of cells from epithelial-like to mesenchymal-like, increased expression levels of mesenchymal markers and decreased expression of epithelial markers. Knockdown of endogenous LIF reverses EMT in cancer cells. We further identified that LIF induces the expression of microRNA-21 (miR-21), which in turn mediates the promoting effect of LIF on EMT. LIF induces miR-21 expression through the activation of STAT3. Importantly, blocking miR-21 function greatly abolished the promoting effect of LIF on EMT and the migration ability of cancer cells. Taken together, results from this study identified an important function and a novel underlying mechanism of LIF in EMT and tumor metastasis. Impact Journals LLC 2015-12-24 /pmc/articles/PMC4826169/ /pubmed/26716902 http://dx.doi.org/10.18632/oncotarget.6756 Text en Copyright: © 2016 Yue et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Yue, Xuetian
Zhao, Yuhan
Zhang, Cen
Li, Jun
Liu, Zhen
Liu, Juan
Hu, Wenwei
Leukemia inhibitory factor promotes EMT through STAT3-dependent miR-21 induction
title Leukemia inhibitory factor promotes EMT through STAT3-dependent miR-21 induction
title_full Leukemia inhibitory factor promotes EMT through STAT3-dependent miR-21 induction
title_fullStr Leukemia inhibitory factor promotes EMT through STAT3-dependent miR-21 induction
title_full_unstemmed Leukemia inhibitory factor promotes EMT through STAT3-dependent miR-21 induction
title_short Leukemia inhibitory factor promotes EMT through STAT3-dependent miR-21 induction
title_sort leukemia inhibitory factor promotes emt through stat3-dependent mir-21 induction
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826169/
https://www.ncbi.nlm.nih.gov/pubmed/26716902
http://dx.doi.org/10.18632/oncotarget.6756
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