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miR-200a-3p- and miR-181-5p-Mediated HOXB5 Upregulation Promotes HCC Progression by Transcriptional Activation of EGFR
BACKGROUND: Hepatocellular carcinoma (HCC) remains a worldwide burden. However, the mechanisms behind the malignant biological behavior of HCC remain unclear. The homeobox (HOX) family could act as either promoters or suppressors in different kinds of malignancies. Our study discovered the role of H...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277860/ https://www.ncbi.nlm.nih.gov/pubmed/35847904 http://dx.doi.org/10.3389/fonc.2022.822760 |
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author | Li, Weizhi Li, Yingchao Li, Peijie Ma, Fuquan Liu, Mengying Kong, Shuzhen Xue, Hui |
author_facet | Li, Weizhi Li, Yingchao Li, Peijie Ma, Fuquan Liu, Mengying Kong, Shuzhen Xue, Hui |
author_sort | Li, Weizhi |
collection | PubMed |
description | BACKGROUND: Hepatocellular carcinoma (HCC) remains a worldwide burden. However, the mechanisms behind the malignant biological behavior of HCC remain unclear. The homeobox (HOX) family could act as either promoters or suppressors in different kinds of malignancies. Our study discovered the role of HOXB5 in regulating HCC progression. METHODS: The HOXB5 expression was assessed by RT-PCR analysis in human HCC samples and cell lines. HOXB5 transcriptional regulation of the EGFR was verified by the luciferase reporter assay and chromatin immunoprecipitation experiment. The oncogenic role of HOXB5 in HCC progression was analyzed by CCK8, colony-forming, and transwell assays. RESULTS: Upregulation of HOXB5 was found in human HCC, and was strongly correlated with HCC tumor size, tumor-nodule metastasis, TNM stage, and relatively unfavorable OS and DFS. Ectopic expression of HOXB5 promoted the capacity of cell growth and clonogenicity, while the inhibition of HOXB5 decreased the proliferation and clonogenicity potential in vitro by CCK8 and colony-forming assays. In addition, HOXB5 also promoted cell migration by transwell experiment. Mechanism studies elucidated that HOXB5 triggers HCC progression via direct transcriptional activation of EGFR. The upregulation of HOXB5 is regulated by miR-200a-3p and miR-181-5p. Transfection of miR-200a-3p and miR-181-5p mimics blocked the cell proliferation and migration regulated by HOXB5, while overexpression of the 3′-UTR mutant HOXB5 abolished the suppressive effect of miR-200a-3p and miR-181-5p, but not the wild-type HOXB5. CONCLUSION: HOXB5 is a promising prognostic factor in human HCC. Targeting miR-200a-3p and the miR-181-5p/HOXB5/EGFR signaling pathway may provide new options for the treatment strategies of HCC. |
format | Online Article Text |
id | pubmed-9277860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92778602022-07-14 miR-200a-3p- and miR-181-5p-Mediated HOXB5 Upregulation Promotes HCC Progression by Transcriptional Activation of EGFR Li, Weizhi Li, Yingchao Li, Peijie Ma, Fuquan Liu, Mengying Kong, Shuzhen Xue, Hui Front Oncol Oncology BACKGROUND: Hepatocellular carcinoma (HCC) remains a worldwide burden. However, the mechanisms behind the malignant biological behavior of HCC remain unclear. The homeobox (HOX) family could act as either promoters or suppressors in different kinds of malignancies. Our study discovered the role of HOXB5 in regulating HCC progression. METHODS: The HOXB5 expression was assessed by RT-PCR analysis in human HCC samples and cell lines. HOXB5 transcriptional regulation of the EGFR was verified by the luciferase reporter assay and chromatin immunoprecipitation experiment. The oncogenic role of HOXB5 in HCC progression was analyzed by CCK8, colony-forming, and transwell assays. RESULTS: Upregulation of HOXB5 was found in human HCC, and was strongly correlated with HCC tumor size, tumor-nodule metastasis, TNM stage, and relatively unfavorable OS and DFS. Ectopic expression of HOXB5 promoted the capacity of cell growth and clonogenicity, while the inhibition of HOXB5 decreased the proliferation and clonogenicity potential in vitro by CCK8 and colony-forming assays. In addition, HOXB5 also promoted cell migration by transwell experiment. Mechanism studies elucidated that HOXB5 triggers HCC progression via direct transcriptional activation of EGFR. The upregulation of HOXB5 is regulated by miR-200a-3p and miR-181-5p. Transfection of miR-200a-3p and miR-181-5p mimics blocked the cell proliferation and migration regulated by HOXB5, while overexpression of the 3′-UTR mutant HOXB5 abolished the suppressive effect of miR-200a-3p and miR-181-5p, but not the wild-type HOXB5. CONCLUSION: HOXB5 is a promising prognostic factor in human HCC. Targeting miR-200a-3p and the miR-181-5p/HOXB5/EGFR signaling pathway may provide new options for the treatment strategies of HCC. Frontiers Media S.A. 2022-06-29 /pmc/articles/PMC9277860/ /pubmed/35847904 http://dx.doi.org/10.3389/fonc.2022.822760 Text en Copyright © 2022 Li, Li, Li, Ma, Liu, Kong and Xue https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Li, Weizhi Li, Yingchao Li, Peijie Ma, Fuquan Liu, Mengying Kong, Shuzhen Xue, Hui miR-200a-3p- and miR-181-5p-Mediated HOXB5 Upregulation Promotes HCC Progression by Transcriptional Activation of EGFR |
title | miR-200a-3p- and miR-181-5p-Mediated HOXB5 Upregulation Promotes HCC Progression by Transcriptional Activation of EGFR |
title_full | miR-200a-3p- and miR-181-5p-Mediated HOXB5 Upregulation Promotes HCC Progression by Transcriptional Activation of EGFR |
title_fullStr | miR-200a-3p- and miR-181-5p-Mediated HOXB5 Upregulation Promotes HCC Progression by Transcriptional Activation of EGFR |
title_full_unstemmed | miR-200a-3p- and miR-181-5p-Mediated HOXB5 Upregulation Promotes HCC Progression by Transcriptional Activation of EGFR |
title_short | miR-200a-3p- and miR-181-5p-Mediated HOXB5 Upregulation Promotes HCC Progression by Transcriptional Activation of EGFR |
title_sort | mir-200a-3p- and mir-181-5p-mediated hoxb5 upregulation promotes hcc progression by transcriptional activation of egfr |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277860/ https://www.ncbi.nlm.nih.gov/pubmed/35847904 http://dx.doi.org/10.3389/fonc.2022.822760 |
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