Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. HCC patients suffer from a high mortality-to-incidence ratio and low cure rate since we still have no specific and effective treatment. Although tremendous advances have been made in the investigation of HCC, the s...

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Autores principales: Hu, Yan-Ting, Li, Bei-Fang, Zhang, Peng-Jun, Wu, Di, Li, Yan-Yan, Li, Zhong-Wu, Shen, Lin, Dong, Bin, Gao, Jing, Zhu, Xu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397724/
https://www.ncbi.nlm.nih.gov/pubmed/30833799
http://dx.doi.org/10.3748/wjg.v25.i8.923
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author Hu, Yan-Ting
Li, Bei-Fang
Zhang, Peng-Jun
Wu, Di
Li, Yan-Yan
Li, Zhong-Wu
Shen, Lin
Dong, Bin
Gao, Jing
Zhu, Xu
author_facet Hu, Yan-Ting
Li, Bei-Fang
Zhang, Peng-Jun
Wu, Di
Li, Yan-Yan
Li, Zhong-Wu
Shen, Lin
Dong, Bin
Gao, Jing
Zhu, Xu
author_sort Hu, Yan-Ting
collection PubMed
description BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. HCC patients suffer from a high mortality-to-incidence ratio and low cure rate since we still have no specific and effective treatment. Although tremendous advances have been made in the investigation of HCC, the specific mechanisms of the progression of this disease are still only partially established. Hence, more research is needed to elucidate the underlying potential mechanisms to develop effective strategies for HCC. AIM: To determine the role of developing brain homeobox 2 (Dbx2) gene in promoting the development of HCC. METHODS: Dbx2 expression in clinical specimens and HCC cell lines was detected by Western blot (WB) and immunohistochemistry. Gain and loss of Dbx2 function assays were performed in vitro and in vivo. Cell viability assays were used to investigate cell growth, flow cytometry was employed to assess cell cycle and apoptosis, and trans-well assays were conducted to evaluate cell migration, invasion, and metastasis. The expression of key molecules in the sonic hedgehog (Shh) signaling was determined by WB. RESULTS: Compared to matched adjacent non-tumorous tissues, Dbx2 was overexpressed in 5 HCC cell lines and 76 surgically resected HCC tissues. Dbx2 overexpression was correlated with large tumor size. Both gain and loss of function assays indicated that Dbx2 promoted HCC cell proliferation by facilitating the transition from G1 to S phase, attenuating apoptosis and promoted HCC proliferation, migration, and invasion in vitro and in vivo. Mechanistically, Dbx2 modulated Shh signaling by enhancing FTCH1 and GLi1 expression in HCC cells that overexpressed Dbx2, which was reversed in HCC cells with Dbx2 knockdown. CONCLUSION: Our results indicate that Dbx2 is significantly upregulated in HCC tissues and plays significant roles in proliferation and metastasis of HCC cells by activating the Shh pathway.
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spelling pubmed-63977242019-03-04 Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling Hu, Yan-Ting Li, Bei-Fang Zhang, Peng-Jun Wu, Di Li, Yan-Yan Li, Zhong-Wu Shen, Lin Dong, Bin Gao, Jing Zhu, Xu World J Gastroenterol Basic Study BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. HCC patients suffer from a high mortality-to-incidence ratio and low cure rate since we still have no specific and effective treatment. Although tremendous advances have been made in the investigation of HCC, the specific mechanisms of the progression of this disease are still only partially established. Hence, more research is needed to elucidate the underlying potential mechanisms to develop effective strategies for HCC. AIM: To determine the role of developing brain homeobox 2 (Dbx2) gene in promoting the development of HCC. METHODS: Dbx2 expression in clinical specimens and HCC cell lines was detected by Western blot (WB) and immunohistochemistry. Gain and loss of Dbx2 function assays were performed in vitro and in vivo. Cell viability assays were used to investigate cell growth, flow cytometry was employed to assess cell cycle and apoptosis, and trans-well assays were conducted to evaluate cell migration, invasion, and metastasis. The expression of key molecules in the sonic hedgehog (Shh) signaling was determined by WB. RESULTS: Compared to matched adjacent non-tumorous tissues, Dbx2 was overexpressed in 5 HCC cell lines and 76 surgically resected HCC tissues. Dbx2 overexpression was correlated with large tumor size. Both gain and loss of function assays indicated that Dbx2 promoted HCC cell proliferation by facilitating the transition from G1 to S phase, attenuating apoptosis and promoted HCC proliferation, migration, and invasion in vitro and in vivo. Mechanistically, Dbx2 modulated Shh signaling by enhancing FTCH1 and GLi1 expression in HCC cells that overexpressed Dbx2, which was reversed in HCC cells with Dbx2 knockdown. CONCLUSION: Our results indicate that Dbx2 is significantly upregulated in HCC tissues and plays significant roles in proliferation and metastasis of HCC cells by activating the Shh pathway. Baishideng Publishing Group Inc 2019-02-28 2019-02-28 /pmc/articles/PMC6397724/ /pubmed/30833799 http://dx.doi.org/10.3748/wjg.v25.i8.923 Text en ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Basic Study
Hu, Yan-Ting
Li, Bei-Fang
Zhang, Peng-Jun
Wu, Di
Li, Yan-Yan
Li, Zhong-Wu
Shen, Lin
Dong, Bin
Gao, Jing
Zhu, Xu
Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling
title Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling
title_full Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling
title_fullStr Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling
title_full_unstemmed Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling
title_short Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling
title_sort dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating shh-gli1 signaling
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397724/
https://www.ncbi.nlm.nih.gov/pubmed/30833799
http://dx.doi.org/10.3748/wjg.v25.i8.923
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