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Targeting LRH-1 in hepatoblastoma cell lines causes decreased proliferation

Hepatoblastoma is the most common malignant liver tumor in children. Since it is often unresectable and exhibits drug resistance, the treatment of advanced hepatoblastoma is challenging. The orphan nuclear receptor liver receptor homolog-1 (LRH-1) serves prominent roles in malignancy; however, to th...

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Autores principales: Jin, Jingling, Jin, Junliang, Woodfield, Sarah E., Patel, Roma H., Jin, Nan Ge, Shi, Yan, Liu, Bin, Sun, Wenjing, Chen, Xiangmei, Yu, Yang, Vasudevan, Sanjeev A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278492/
https://www.ncbi.nlm.nih.gov/pubmed/30320362
http://dx.doi.org/10.3892/or.2018.6793
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author Jin, Jingling
Jin, Junliang
Woodfield, Sarah E.
Patel, Roma H.
Jin, Nan Ge
Shi, Yan
Liu, Bin
Sun, Wenjing
Chen, Xiangmei
Yu, Yang
Vasudevan, Sanjeev A.
author_facet Jin, Jingling
Jin, Junliang
Woodfield, Sarah E.
Patel, Roma H.
Jin, Nan Ge
Shi, Yan
Liu, Bin
Sun, Wenjing
Chen, Xiangmei
Yu, Yang
Vasudevan, Sanjeev A.
author_sort Jin, Jingling
collection PubMed
description Hepatoblastoma is the most common malignant liver tumor in children. Since it is often unresectable and exhibits drug resistance, the treatment of advanced hepatoblastoma is challenging. The orphan nuclear receptor liver receptor homolog-1 (LRH-1) serves prominent roles in malignancy; however, to the best of our knowledge, the role of LRH-1 in hepatoblastoma remains unknown. In the present study, human hepatoblastoma cell lines were analyzed; the mRNA and protein expression levels of LRH-1 were significantly higher in HepG2 and HuH6 cells compared with those in HepT1 cells and control THLE-2 cells. Knockdown of LRH-1 resulted in decreased HepG2 and HuH6 cell proliferation via downregulation of cyclin D1 (CCND1) and c-Myc. Furthermore, treatment with an LRH-1 antagonist (LRA) inhibited the proliferation and colony formation of cell lines in a dose-dependent manner, and induced cell cycle arrest at G(1) phase through inhibition of CCND1 expression. Finally, LRA treatment enhanced the cytotoxic effects of doxorubicin on hepatoblastoma cells. Collectively, these findings suggested that LRH-1 may have an important role in the progression of hepatoblastoma and implicated LRA as a novel, potential therapeutic agent for the treatment of hepatoblastoma.
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spelling pubmed-62784922018-12-17 Targeting LRH-1 in hepatoblastoma cell lines causes decreased proliferation Jin, Jingling Jin, Junliang Woodfield, Sarah E. Patel, Roma H. Jin, Nan Ge Shi, Yan Liu, Bin Sun, Wenjing Chen, Xiangmei Yu, Yang Vasudevan, Sanjeev A. Oncol Rep Articles Hepatoblastoma is the most common malignant liver tumor in children. Since it is often unresectable and exhibits drug resistance, the treatment of advanced hepatoblastoma is challenging. The orphan nuclear receptor liver receptor homolog-1 (LRH-1) serves prominent roles in malignancy; however, to the best of our knowledge, the role of LRH-1 in hepatoblastoma remains unknown. In the present study, human hepatoblastoma cell lines were analyzed; the mRNA and protein expression levels of LRH-1 were significantly higher in HepG2 and HuH6 cells compared with those in HepT1 cells and control THLE-2 cells. Knockdown of LRH-1 resulted in decreased HepG2 and HuH6 cell proliferation via downregulation of cyclin D1 (CCND1) and c-Myc. Furthermore, treatment with an LRH-1 antagonist (LRA) inhibited the proliferation and colony formation of cell lines in a dose-dependent manner, and induced cell cycle arrest at G(1) phase through inhibition of CCND1 expression. Finally, LRA treatment enhanced the cytotoxic effects of doxorubicin on hepatoblastoma cells. Collectively, these findings suggested that LRH-1 may have an important role in the progression of hepatoblastoma and implicated LRA as a novel, potential therapeutic agent for the treatment of hepatoblastoma. D.A. Spandidos 2019-01 2018-10-15 /pmc/articles/PMC6278492/ /pubmed/30320362 http://dx.doi.org/10.3892/or.2018.6793 Text en Copyright: © Jin et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Jin, Jingling
Jin, Junliang
Woodfield, Sarah E.
Patel, Roma H.
Jin, Nan Ge
Shi, Yan
Liu, Bin
Sun, Wenjing
Chen, Xiangmei
Yu, Yang
Vasudevan, Sanjeev A.
Targeting LRH-1 in hepatoblastoma cell lines causes decreased proliferation
title Targeting LRH-1 in hepatoblastoma cell lines causes decreased proliferation
title_full Targeting LRH-1 in hepatoblastoma cell lines causes decreased proliferation
title_fullStr Targeting LRH-1 in hepatoblastoma cell lines causes decreased proliferation
title_full_unstemmed Targeting LRH-1 in hepatoblastoma cell lines causes decreased proliferation
title_short Targeting LRH-1 in hepatoblastoma cell lines causes decreased proliferation
title_sort targeting lrh-1 in hepatoblastoma cell lines causes decreased proliferation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278492/
https://www.ncbi.nlm.nih.gov/pubmed/30320362
http://dx.doi.org/10.3892/or.2018.6793
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