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LncZEB1-AS1 regulates hepatocellular carcinoma bone metastasis via regulation of the miR-302b-EGFR-PI3K-AKT axis
In patients with hepatocellular carcinoma (HCC), disease progression and associated bone metastasis (BM) can markedly reduce quality of life. While the long non-coding RNA (lncRNA) zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) has been shown to function as a key regulator of oncogenic...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378930/ https://www.ncbi.nlm.nih.gov/pubmed/32742459 http://dx.doi.org/10.7150/jca.45995 |
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author | Ma, Zhen-jiang Wang, Yao Li, Hui-fen Liu, Ming-Hua Bi, Feng-rui Ma, Long Ma, Hui Yan, Hong-li |
author_facet | Ma, Zhen-jiang Wang, Yao Li, Hui-fen Liu, Ming-Hua Bi, Feng-rui Ma, Long Ma, Hui Yan, Hong-li |
author_sort | Ma, Zhen-jiang |
collection | PubMed |
description | In patients with hepatocellular carcinoma (HCC), disease progression and associated bone metastasis (BM) can markedly reduce quality of life. While the long non-coding RNA (lncRNA) zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) has been shown to function as a key regulator of oncogenic processes in HCC and other tumor types, whether it plays a role in controlling HCC BM remains to be established. In the current study, we detected the significant upregulation of lncZEB1-AS1 in HCC tissues, and we found this expression to be associated with BM progression. When we knocked down this lncRNA in HCC cells, we found that this significantly reduced their migratory, invasive, and metastatic activity both in vitro and in vivo. At a mechanistic level, we found that lncZEB1-AS1 was able to target miR-302b and to thereby increase PI3K-AKT pathway activation and EGFR expression, resulting in the enhanced expression of downstream matrix metalloproteinase genes in HCC cells. In summary, our results provide novel evidence that lncZEB1-AS1 can promote HCC BM through a mechanism dependent upon the activation of PI3K-AKT signaling, thus highlighting a potentially novel therapeutic avenue for the treatment of such metastatic progression in HCC patients. |
format | Online Article Text |
id | pubmed-7378930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-73789302020-07-30 LncZEB1-AS1 regulates hepatocellular carcinoma bone metastasis via regulation of the miR-302b-EGFR-PI3K-AKT axis Ma, Zhen-jiang Wang, Yao Li, Hui-fen Liu, Ming-Hua Bi, Feng-rui Ma, Long Ma, Hui Yan, Hong-li J Cancer Research Paper In patients with hepatocellular carcinoma (HCC), disease progression and associated bone metastasis (BM) can markedly reduce quality of life. While the long non-coding RNA (lncRNA) zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) has been shown to function as a key regulator of oncogenic processes in HCC and other tumor types, whether it plays a role in controlling HCC BM remains to be established. In the current study, we detected the significant upregulation of lncZEB1-AS1 in HCC tissues, and we found this expression to be associated with BM progression. When we knocked down this lncRNA in HCC cells, we found that this significantly reduced their migratory, invasive, and metastatic activity both in vitro and in vivo. At a mechanistic level, we found that lncZEB1-AS1 was able to target miR-302b and to thereby increase PI3K-AKT pathway activation and EGFR expression, resulting in the enhanced expression of downstream matrix metalloproteinase genes in HCC cells. In summary, our results provide novel evidence that lncZEB1-AS1 can promote HCC BM through a mechanism dependent upon the activation of PI3K-AKT signaling, thus highlighting a potentially novel therapeutic avenue for the treatment of such metastatic progression in HCC patients. Ivyspring International Publisher 2020-06-28 /pmc/articles/PMC7378930/ /pubmed/32742459 http://dx.doi.org/10.7150/jca.45995 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Ma, Zhen-jiang Wang, Yao Li, Hui-fen Liu, Ming-Hua Bi, Feng-rui Ma, Long Ma, Hui Yan, Hong-li LncZEB1-AS1 regulates hepatocellular carcinoma bone metastasis via regulation of the miR-302b-EGFR-PI3K-AKT axis |
title | LncZEB1-AS1 regulates hepatocellular carcinoma bone metastasis via regulation of the miR-302b-EGFR-PI3K-AKT axis |
title_full | LncZEB1-AS1 regulates hepatocellular carcinoma bone metastasis via regulation of the miR-302b-EGFR-PI3K-AKT axis |
title_fullStr | LncZEB1-AS1 regulates hepatocellular carcinoma bone metastasis via regulation of the miR-302b-EGFR-PI3K-AKT axis |
title_full_unstemmed | LncZEB1-AS1 regulates hepatocellular carcinoma bone metastasis via regulation of the miR-302b-EGFR-PI3K-AKT axis |
title_short | LncZEB1-AS1 regulates hepatocellular carcinoma bone metastasis via regulation of the miR-302b-EGFR-PI3K-AKT axis |
title_sort | lnczeb1-as1 regulates hepatocellular carcinoma bone metastasis via regulation of the mir-302b-egfr-pi3k-akt axis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378930/ https://www.ncbi.nlm.nih.gov/pubmed/32742459 http://dx.doi.org/10.7150/jca.45995 |
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