Cargando…
Promoter Hypomethylation and miR-145-5p Downregulation- Mediated HDAC11 Overexpression Promotes Sorafenib Resistance and Metastasis of Hepatocellular Carcinoma Cells
Sorafenib resistance and tumor metastasis account for poor outcome of hepatocellular carcinoma (HCC). Histone deacetylase 11 (HDAC11) has been reported to exert oncogenic effects in several types of human cancer, but its specific functions and detailed mechanisms in HCC are not fully elucidated. Her...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434871/ https://www.ncbi.nlm.nih.gov/pubmed/32903337 http://dx.doi.org/10.3389/fcell.2020.00724 |
_version_ | 1783572227279552512 |
---|---|
author | Wang, Wenlong Ding, Bisha Lou, Weiyang Lin, Shengyou |
author_facet | Wang, Wenlong Ding, Bisha Lou, Weiyang Lin, Shengyou |
author_sort | Wang, Wenlong |
collection | PubMed |
description | Sorafenib resistance and tumor metastasis account for poor outcome of hepatocellular carcinoma (HCC). Histone deacetylase 11 (HDAC11) has been reported to exert oncogenic effects in several types of human cancer, but its specific functions and detailed mechanisms in HCC are not fully elucidated. Here we identified HDAC11 as a potential oncogene and promising biomarker in HCC by in silico analysis. Histone deacetylase 11 was upregulated in sorafenib-resistant SMMC7721 compared with its parental cell. Knockdown of HDAC11 suppressed proliferation and sorafenib resistance, which may be due to inhibition of drug metabolism cytochrome P450 predicted by gene-set enrichment analysis. Histone deacetylase expression was higher in highly metastatic MHCC97H than lowly metastatic MHCC97L. Downregulation of HDAC11 significantly attenuated the migrated and invaded abilities of HCC cells. Histone deacetylase 11 was directly targeted and suppressed by miR-145-5p. Inhibition of miR-145-5p enhanced sorafenib resistance and metastasis of HCC, and these effects could be attenuated by knockdown of HDAC11. The promoter methylation level of HDAC11 was markedly decreased in HCC tissues compared with normal controls. Administration of 5’-Aza-2’-deoxycytidine, a DNA methyltransferase inhibitor, facilitated HDAC11 expression in HCC cells. Our data indicate a role of miR-145-5p/HDAC11 axis in regulation of sorafenib resistance and metastasis in HCC. |
format | Online Article Text |
id | pubmed-7434871 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74348712020-09-03 Promoter Hypomethylation and miR-145-5p Downregulation- Mediated HDAC11 Overexpression Promotes Sorafenib Resistance and Metastasis of Hepatocellular Carcinoma Cells Wang, Wenlong Ding, Bisha Lou, Weiyang Lin, Shengyou Front Cell Dev Biol Cell and Developmental Biology Sorafenib resistance and tumor metastasis account for poor outcome of hepatocellular carcinoma (HCC). Histone deacetylase 11 (HDAC11) has been reported to exert oncogenic effects in several types of human cancer, but its specific functions and detailed mechanisms in HCC are not fully elucidated. Here we identified HDAC11 as a potential oncogene and promising biomarker in HCC by in silico analysis. Histone deacetylase 11 was upregulated in sorafenib-resistant SMMC7721 compared with its parental cell. Knockdown of HDAC11 suppressed proliferation and sorafenib resistance, which may be due to inhibition of drug metabolism cytochrome P450 predicted by gene-set enrichment analysis. Histone deacetylase expression was higher in highly metastatic MHCC97H than lowly metastatic MHCC97L. Downregulation of HDAC11 significantly attenuated the migrated and invaded abilities of HCC cells. Histone deacetylase 11 was directly targeted and suppressed by miR-145-5p. Inhibition of miR-145-5p enhanced sorafenib resistance and metastasis of HCC, and these effects could be attenuated by knockdown of HDAC11. The promoter methylation level of HDAC11 was markedly decreased in HCC tissues compared with normal controls. Administration of 5’-Aza-2’-deoxycytidine, a DNA methyltransferase inhibitor, facilitated HDAC11 expression in HCC cells. Our data indicate a role of miR-145-5p/HDAC11 axis in regulation of sorafenib resistance and metastasis in HCC. Frontiers Media S.A. 2020-08-12 /pmc/articles/PMC7434871/ /pubmed/32903337 http://dx.doi.org/10.3389/fcell.2020.00724 Text en Copyright © 2020 Wang, Ding, Lou and Lin. http://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 | Cell and Developmental Biology Wang, Wenlong Ding, Bisha Lou, Weiyang Lin, Shengyou Promoter Hypomethylation and miR-145-5p Downregulation- Mediated HDAC11 Overexpression Promotes Sorafenib Resistance and Metastasis of Hepatocellular Carcinoma Cells |
title | Promoter Hypomethylation and miR-145-5p Downregulation- Mediated HDAC11 Overexpression Promotes Sorafenib Resistance and Metastasis of Hepatocellular Carcinoma Cells |
title_full | Promoter Hypomethylation and miR-145-5p Downregulation- Mediated HDAC11 Overexpression Promotes Sorafenib Resistance and Metastasis of Hepatocellular Carcinoma Cells |
title_fullStr | Promoter Hypomethylation and miR-145-5p Downregulation- Mediated HDAC11 Overexpression Promotes Sorafenib Resistance and Metastasis of Hepatocellular Carcinoma Cells |
title_full_unstemmed | Promoter Hypomethylation and miR-145-5p Downregulation- Mediated HDAC11 Overexpression Promotes Sorafenib Resistance and Metastasis of Hepatocellular Carcinoma Cells |
title_short | Promoter Hypomethylation and miR-145-5p Downregulation- Mediated HDAC11 Overexpression Promotes Sorafenib Resistance and Metastasis of Hepatocellular Carcinoma Cells |
title_sort | promoter hypomethylation and mir-145-5p downregulation- mediated hdac11 overexpression promotes sorafenib resistance and metastasis of hepatocellular carcinoma cells |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434871/ https://www.ncbi.nlm.nih.gov/pubmed/32903337 http://dx.doi.org/10.3389/fcell.2020.00724 |
work_keys_str_mv | AT wangwenlong promoterhypomethylationandmir1455pdownregulationmediatedhdac11overexpressionpromotessorafenibresistanceandmetastasisofhepatocellularcarcinomacells AT dingbisha promoterhypomethylationandmir1455pdownregulationmediatedhdac11overexpressionpromotessorafenibresistanceandmetastasisofhepatocellularcarcinomacells AT louweiyang promoterhypomethylationandmir1455pdownregulationmediatedhdac11overexpressionpromotessorafenibresistanceandmetastasisofhepatocellularcarcinomacells AT linshengyou promoterhypomethylationandmir1455pdownregulationmediatedhdac11overexpressionpromotessorafenibresistanceandmetastasisofhepatocellularcarcinomacells |