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Long non-coding RNA CASC2 enhances berberine-induced cytotoxicity in colorectal cancer cells by silencing BCL2
Berberine, a natural isoquinoline alkaloid derived from Berberis species, has been reported to have anticancer effects. However, the mechanisms of action in human colorectal cancer (CRC) are not well established to date. In the present study, the cell cytotoxicity effect of berberine on human CRC ce...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625213/ https://www.ncbi.nlm.nih.gov/pubmed/31173223 http://dx.doi.org/10.3892/mmr.2019.10326 |
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author | Dai, Wei Mu, Liyuan Cui, Yali Li, Yingying Chen, Ping Xie, Hongjian Wang, Xia |
author_facet | Dai, Wei Mu, Liyuan Cui, Yali Li, Yingying Chen, Ping Xie, Hongjian Wang, Xia |
author_sort | Dai, Wei |
collection | PubMed |
description | Berberine, a natural isoquinoline alkaloid derived from Berberis species, has been reported to have anticancer effects. However, the mechanisms of action in human colorectal cancer (CRC) are not well established to date. In the present study, the cell cytotoxicity effect of berberine on human CRC cells, as well as the possible mechanisms involved, was investigated. The results of the cell viability and apoptosis assay revealed that treatment of CRC cells with berberine resulted in inhibition of cell viability and activation of cell apoptosis in a concentration-dependent manner. To reveal the underlying mechanism of berberine-induced anti-tumor activity and cell apoptosis, RNA-sequencing followed by reverse-transcription quantitative PCR were performed. In addition, RNA immunoprecipitation, chromatin immunoprecipitation and western blot analysis were used to identify the functional regulation of CASC2/EZH2/BCL2 axis in berberine-induced CRC cell apoptosis. The data revealed that lncRNA CASC2 was upregulated by berberine treatment. Gain- or loss-of-function assays suggested that lncRNA CASC2 was required for the berberine-induced inhibition of cell viability and activation of cell apoptosis. Subsequently, the downstream antiapoptotic gene BCL2 was identified as a functional target of the berberine/CASC2 mechanism, as BCL2 reversed the berberine/CASC2-induced cell cytotoxicity. lncRNA CASC2 silenced BCL2 expression by binding to the promoter region of BCL2 in an EZH2-dependent manner. In summary, berberine may be a novel therapeutic agent for CRC and lncRNA CASC2 may serve as an important therapeutic target to improve the anticancer effect of berberine. |
format | Online Article Text |
id | pubmed-6625213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-66252132019-07-31 Long non-coding RNA CASC2 enhances berberine-induced cytotoxicity in colorectal cancer cells by silencing BCL2 Dai, Wei Mu, Liyuan Cui, Yali Li, Yingying Chen, Ping Xie, Hongjian Wang, Xia Mol Med Rep Articles Berberine, a natural isoquinoline alkaloid derived from Berberis species, has been reported to have anticancer effects. However, the mechanisms of action in human colorectal cancer (CRC) are not well established to date. In the present study, the cell cytotoxicity effect of berberine on human CRC cells, as well as the possible mechanisms involved, was investigated. The results of the cell viability and apoptosis assay revealed that treatment of CRC cells with berberine resulted in inhibition of cell viability and activation of cell apoptosis in a concentration-dependent manner. To reveal the underlying mechanism of berberine-induced anti-tumor activity and cell apoptosis, RNA-sequencing followed by reverse-transcription quantitative PCR were performed. In addition, RNA immunoprecipitation, chromatin immunoprecipitation and western blot analysis were used to identify the functional regulation of CASC2/EZH2/BCL2 axis in berberine-induced CRC cell apoptosis. The data revealed that lncRNA CASC2 was upregulated by berberine treatment. Gain- or loss-of-function assays suggested that lncRNA CASC2 was required for the berberine-induced inhibition of cell viability and activation of cell apoptosis. Subsequently, the downstream antiapoptotic gene BCL2 was identified as a functional target of the berberine/CASC2 mechanism, as BCL2 reversed the berberine/CASC2-induced cell cytotoxicity. lncRNA CASC2 silenced BCL2 expression by binding to the promoter region of BCL2 in an EZH2-dependent manner. In summary, berberine may be a novel therapeutic agent for CRC and lncRNA CASC2 may serve as an important therapeutic target to improve the anticancer effect of berberine. D.A. Spandidos 2019-08 2019-06-03 /pmc/articles/PMC6625213/ /pubmed/31173223 http://dx.doi.org/10.3892/mmr.2019.10326 Text en Copyright: © Dai et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Dai, Wei Mu, Liyuan Cui, Yali Li, Yingying Chen, Ping Xie, Hongjian Wang, Xia Long non-coding RNA CASC2 enhances berberine-induced cytotoxicity in colorectal cancer cells by silencing BCL2 |
title | Long non-coding RNA CASC2 enhances berberine-induced cytotoxicity in colorectal cancer cells by silencing BCL2 |
title_full | Long non-coding RNA CASC2 enhances berberine-induced cytotoxicity in colorectal cancer cells by silencing BCL2 |
title_fullStr | Long non-coding RNA CASC2 enhances berberine-induced cytotoxicity in colorectal cancer cells by silencing BCL2 |
title_full_unstemmed | Long non-coding RNA CASC2 enhances berberine-induced cytotoxicity in colorectal cancer cells by silencing BCL2 |
title_short | Long non-coding RNA CASC2 enhances berberine-induced cytotoxicity in colorectal cancer cells by silencing BCL2 |
title_sort | long non-coding rna casc2 enhances berberine-induced cytotoxicity in colorectal cancer cells by silencing bcl2 |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625213/ https://www.ncbi.nlm.nih.gov/pubmed/31173223 http://dx.doi.org/10.3892/mmr.2019.10326 |
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