Cargando…
Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1 In Vivo
PURPOSE: Multidrug resistance (MDR) remains a major obstacle in the treatment of triple-negative breast cancer (TNBC) with conventional chemotherapeutic agents. A previous study demonstrated that hsa-miRNA-143-3p plays a vital role in drug resistance of TNBC. Downregulation of hsa-miRNA-143-3p upreg...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Breast Cancer Society
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158160/ https://www.ncbi.nlm.nih.gov/pubmed/30275853 http://dx.doi.org/10.4048/jbc.2018.21.e40 |
_version_ | 1783358372377001984 |
---|---|
author | Deng, Yu Wei Hao, Wen Jing Li, Yi Wen Li, Yi Xin Zhao, Bo Chen Lu, Dan |
author_facet | Deng, Yu Wei Hao, Wen Jing Li, Yi Wen Li, Yi Xin Zhao, Bo Chen Lu, Dan |
author_sort | Deng, Yu Wei |
collection | PubMed |
description | PURPOSE: Multidrug resistance (MDR) remains a major obstacle in the treatment of triple-negative breast cancer (TNBC) with conventional chemotherapeutic agents. A previous study demonstrated that hsa-miRNA-143-3p plays a vital role in drug resistance of TNBC. Downregulation of hsa-miRNA-143-3p upregulated the expression of its target protein cytokine-induced apoptosis inhibitor 1 (CIAPIN1) in order to activate MDR, while upregulation of hsa-miRNA-143-3p effectively enhances the sensitivity of drug-resistant TNBC cells to chemotherapeutics. The present study aimed to further verify these findings in vivo. METHODS: We established a hypodermic tumor nude mice model using paclitaxel-resistant TNBC cells. We expressed ectopic hsa-miRNA-143-3p under the control of a breast cancer-specific human mammaglobin promoter that guided the efficient expression of exogenous hsa-miRNA-143-3p only in breast cancer cells. Thereafter, we overexpressed hsa-miRNA-143-3p in xenografts using a recombinant virus system and quantified the expression of hsa-miRNA-143-3p, CIAPIN1 protein, and proteins encoded by related functional genes by western blot. RESULTS: We successfully completed the prospective exploration of the intravenous virus injection pattern from extensive expression to targeted expression. The overexpression of hsa-miRNA-143-3p significantly alleviated chemoresistance of TNBC by inhibiting viability. In addition, we observed that the expression of CIAPIN1 as a hsa-miRNA-143-3p target protein was remarkably decreased. CONCLUSION: We partly illustrated the mechanism underlying the hsa-miRNA-143-3p/CIAPIN1 drug resistance pathway. HsamiRNA-143-3p as a tumor suppressive microRNA may be a novel target to effectively reverse MDR of TNBC in vivo. |
format | Online Article Text |
id | pubmed-6158160 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Korean Breast Cancer Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-61581602018-10-01 Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1 In Vivo Deng, Yu Wei Hao, Wen Jing Li, Yi Wen Li, Yi Xin Zhao, Bo Chen Lu, Dan J Breast Cancer Original Article PURPOSE: Multidrug resistance (MDR) remains a major obstacle in the treatment of triple-negative breast cancer (TNBC) with conventional chemotherapeutic agents. A previous study demonstrated that hsa-miRNA-143-3p plays a vital role in drug resistance of TNBC. Downregulation of hsa-miRNA-143-3p upregulated the expression of its target protein cytokine-induced apoptosis inhibitor 1 (CIAPIN1) in order to activate MDR, while upregulation of hsa-miRNA-143-3p effectively enhances the sensitivity of drug-resistant TNBC cells to chemotherapeutics. The present study aimed to further verify these findings in vivo. METHODS: We established a hypodermic tumor nude mice model using paclitaxel-resistant TNBC cells. We expressed ectopic hsa-miRNA-143-3p under the control of a breast cancer-specific human mammaglobin promoter that guided the efficient expression of exogenous hsa-miRNA-143-3p only in breast cancer cells. Thereafter, we overexpressed hsa-miRNA-143-3p in xenografts using a recombinant virus system and quantified the expression of hsa-miRNA-143-3p, CIAPIN1 protein, and proteins encoded by related functional genes by western blot. RESULTS: We successfully completed the prospective exploration of the intravenous virus injection pattern from extensive expression to targeted expression. The overexpression of hsa-miRNA-143-3p significantly alleviated chemoresistance of TNBC by inhibiting viability. In addition, we observed that the expression of CIAPIN1 as a hsa-miRNA-143-3p target protein was remarkably decreased. CONCLUSION: We partly illustrated the mechanism underlying the hsa-miRNA-143-3p/CIAPIN1 drug resistance pathway. HsamiRNA-143-3p as a tumor suppressive microRNA may be a novel target to effectively reverse MDR of TNBC in vivo. Korean Breast Cancer Society 2018-09 2018-09-12 /pmc/articles/PMC6158160/ /pubmed/30275853 http://dx.doi.org/10.4048/jbc.2018.21.e40 Text en © 2018 Korean Breast Cancer Society http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Deng, Yu Wei Hao, Wen Jing Li, Yi Wen Li, Yi Xin Zhao, Bo Chen Lu, Dan Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1 In Vivo |
title | Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1 In Vivo |
title_full | Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1 In Vivo |
title_fullStr | Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1 In Vivo |
title_full_unstemmed | Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1 In Vivo |
title_short | Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1 In Vivo |
title_sort | hsa-mirna-143-3p reverses multidrug resistance of triple-negative breast cancer by inhibiting the expression of its target protein cytokine-induced apoptosis inhibitor 1 in vivo |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158160/ https://www.ncbi.nlm.nih.gov/pubmed/30275853 http://dx.doi.org/10.4048/jbc.2018.21.e40 |
work_keys_str_mv | AT dengyuwei hsamirna1433preversesmultidrugresistanceoftriplenegativebreastcancerbyinhibitingtheexpressionofitstargetproteincytokineinducedapoptosisinhibitor1invivo AT haowenjing hsamirna1433preversesmultidrugresistanceoftriplenegativebreastcancerbyinhibitingtheexpressionofitstargetproteincytokineinducedapoptosisinhibitor1invivo AT liyiwen hsamirna1433preversesmultidrugresistanceoftriplenegativebreastcancerbyinhibitingtheexpressionofitstargetproteincytokineinducedapoptosisinhibitor1invivo AT liyixin hsamirna1433preversesmultidrugresistanceoftriplenegativebreastcancerbyinhibitingtheexpressionofitstargetproteincytokineinducedapoptosisinhibitor1invivo AT zhaobochen hsamirna1433preversesmultidrugresistanceoftriplenegativebreastcancerbyinhibitingtheexpressionofitstargetproteincytokineinducedapoptosisinhibitor1invivo AT ludan hsamirna1433preversesmultidrugresistanceoftriplenegativebreastcancerbyinhibitingtheexpressionofitstargetproteincytokineinducedapoptosisinhibitor1invivo |