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Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits the growth and invasion of hepatocellular carcinoma via down-regulating midkine expression
The insulin-like growth factor-1 receptor (IGF-1R) overexpression contributes to the development of a variety of cancers. The present study explored the role of IGF-1R in the development and progression of hepatocellular carcinoma (HCC) and the possibility of IGF-1R silencing by lentivirus-mediated...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346715/ https://www.ncbi.nlm.nih.gov/pubmed/27813495 http://dx.doi.org/10.18632/oncotarget.13027 |
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author | Bie, Cai Qun Liu, Xu You Cao, Ming Rong Huang, Qiu Yan Tang, Hui Jun Wang, Min Cao, Guo Li Yi, Ting Zhuang Wu, Sheng Lan Xu, Wei Jie Tang, Shao Hui |
author_facet | Bie, Cai Qun Liu, Xu You Cao, Ming Rong Huang, Qiu Yan Tang, Hui Jun Wang, Min Cao, Guo Li Yi, Ting Zhuang Wu, Sheng Lan Xu, Wei Jie Tang, Shao Hui |
author_sort | Bie, Cai Qun |
collection | PubMed |
description | The insulin-like growth factor-1 receptor (IGF-1R) overexpression contributes to the development of a variety of cancers. The present study explored the role of IGF-1R in the development and progression of hepatocellular carcinoma (HCC) and the possibility of IGF-1R silencing by lentivirus-mediated RNA interference (RNAi) as a therapeutic target for HCC. We showed that IGF-1R mRNA was up-regulated in Huh7 and Hep3B cells and human HCC tissues, and that IGF-1R knockdown by RNAi led to decreased proliferation, apoptosis induction, and decreased migration and invasion of Huh7 and Hep3B cells. Further, the in vivo study indicated that IGF-1R knockdown markedly diminished the tumorigenesis and metastasis of Huh7 xenograft. Moreover, the intratumoral administration of lentivirus-IGF-1R siRNA led to significant tumor growth inhibition in an established Huh7 xenograft model. Mechanistic investigations showed that midkine was found to be the most significantly down-regulated protein in Huh7 cells with IGF-1R knockdown, and ectopic overexpression of midkine significantly rescued inhibition of Huh7 cell proliferation, migration, and invasion caused by IGF-1R suppression. Collectively, these data suggest that IGF-1R inhibition by RNAi can significantly suppress HCC growth and invasion at least partially through down-regulating midkine expression, and IGF-1R is a potential target for HCC gene therapy. |
format | Online Article Text |
id | pubmed-5346715 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53467152017-03-30 Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits the growth and invasion of hepatocellular carcinoma via down-regulating midkine expression Bie, Cai Qun Liu, Xu You Cao, Ming Rong Huang, Qiu Yan Tang, Hui Jun Wang, Min Cao, Guo Li Yi, Ting Zhuang Wu, Sheng Lan Xu, Wei Jie Tang, Shao Hui Oncotarget Research Paper The insulin-like growth factor-1 receptor (IGF-1R) overexpression contributes to the development of a variety of cancers. The present study explored the role of IGF-1R in the development and progression of hepatocellular carcinoma (HCC) and the possibility of IGF-1R silencing by lentivirus-mediated RNA interference (RNAi) as a therapeutic target for HCC. We showed that IGF-1R mRNA was up-regulated in Huh7 and Hep3B cells and human HCC tissues, and that IGF-1R knockdown by RNAi led to decreased proliferation, apoptosis induction, and decreased migration and invasion of Huh7 and Hep3B cells. Further, the in vivo study indicated that IGF-1R knockdown markedly diminished the tumorigenesis and metastasis of Huh7 xenograft. Moreover, the intratumoral administration of lentivirus-IGF-1R siRNA led to significant tumor growth inhibition in an established Huh7 xenograft model. Mechanistic investigations showed that midkine was found to be the most significantly down-regulated protein in Huh7 cells with IGF-1R knockdown, and ectopic overexpression of midkine significantly rescued inhibition of Huh7 cell proliferation, migration, and invasion caused by IGF-1R suppression. Collectively, these data suggest that IGF-1R inhibition by RNAi can significantly suppress HCC growth and invasion at least partially through down-regulating midkine expression, and IGF-1R is a potential target for HCC gene therapy. Impact Journals LLC 2016-11-02 /pmc/articles/PMC5346715/ /pubmed/27813495 http://dx.doi.org/10.18632/oncotarget.13027 Text en Copyright: © 2016 Bie et al. http://creativecommons.org/licenses/by/3.0/ 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 Bie, Cai Qun Liu, Xu You Cao, Ming Rong Huang, Qiu Yan Tang, Hui Jun Wang, Min Cao, Guo Li Yi, Ting Zhuang Wu, Sheng Lan Xu, Wei Jie Tang, Shao Hui Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits the growth and invasion of hepatocellular carcinoma via down-regulating midkine expression |
title | Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits the growth and invasion of hepatocellular carcinoma via down-regulating midkine expression |
title_full | Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits the growth and invasion of hepatocellular carcinoma via down-regulating midkine expression |
title_fullStr | Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits the growth and invasion of hepatocellular carcinoma via down-regulating midkine expression |
title_full_unstemmed | Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits the growth and invasion of hepatocellular carcinoma via down-regulating midkine expression |
title_short | Lentivirus-mediated RNAi knockdown of insulin-like growth factor-1 receptor inhibits the growth and invasion of hepatocellular carcinoma via down-regulating midkine expression |
title_sort | lentivirus-mediated rnai knockdown of insulin-like growth factor-1 receptor inhibits the growth and invasion of hepatocellular carcinoma via down-regulating midkine expression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346715/ https://www.ncbi.nlm.nih.gov/pubmed/27813495 http://dx.doi.org/10.18632/oncotarget.13027 |
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