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MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells

The existence of cancer stem cells (CSCs) is the main reason for failure of cancer treatment caused by drug resistance. Therefore, eradicating cancers by targeting CSCs remains a significant challenge. In the present study, because of the important role of BMI-1 proto-oncogene, polycomb ring finger...

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Autores principales: Koh, Hyebin, Park, Hyeri, Chandimali, Nisansala, Huynh, Do Luong, Zhang, Jiao Jiao, Ghosh, Mrinmoy, Gera, Meeta, Kim, Nameun, Bak, Yesol, Yoon, Do-Young, Park, Yang Ho, Kwon, Taeho, Jeong, Dong Kee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746402/
https://www.ncbi.nlm.nih.gov/pubmed/29299167
http://dx.doi.org/10.18632/oncotarget.22818
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author Koh, Hyebin
Park, Hyeri
Chandimali, Nisansala
Huynh, Do Luong
Zhang, Jiao Jiao
Ghosh, Mrinmoy
Gera, Meeta
Kim, Nameun
Bak, Yesol
Yoon, Do-Young
Park, Yang Ho
Kwon, Taeho
Jeong, Dong Kee
author_facet Koh, Hyebin
Park, Hyeri
Chandimali, Nisansala
Huynh, Do Luong
Zhang, Jiao Jiao
Ghosh, Mrinmoy
Gera, Meeta
Kim, Nameun
Bak, Yesol
Yoon, Do-Young
Park, Yang Ho
Kwon, Taeho
Jeong, Dong Kee
author_sort Koh, Hyebin
collection PubMed
description The existence of cancer stem cells (CSCs) is the main reason for failure of cancer treatment caused by drug resistance. Therefore, eradicating cancers by targeting CSCs remains a significant challenge. In the present study, because of the important role of BMI-1 proto-oncogene, polycomb ring finger (BMI-1) and C-terminal Mucin1 (MUC1-C) in tumor growth and maintenance of CSCs, we aimed to confirm that microRNA miR-128, as an inhibitor of BMI-1 and MUC1-C, could effectively suppress paclitaxel (PTX)-resistant lung cancer stem cells. We showed that CSCs have significantly higher expression levels of BMI-1, MUC1-C, stemness proteins, signaling factors, and higher malignancy compared with normal tumor cells. After transfection with miR-128, the BMI-1 and MUC1-C levels in CSCs were suppressed. When miR-128 was stably expressed in PTX-resistant lung cancer stem cells, the cells showed decreased proliferation, metastasis, self-renewal, migration, invasive ability, clonogenicity, and tumorigenicity in vitro and in vivo and increased apoptosis compared with miR-NC (negative control) CSCs. Furthermore, miR-128 effectively decreased the levels of β-catenin and intracellular signaling pathway-related factors in CSCs. MiR-128 also decreased the luciferase activity of MUC1 reporter constructs and reduced the levels of transmembrane MUC1-C and BMI-1. These results suggested miR-128 as an attractive therapeutic strategy for PTX-resistant lung cancer via inhibition of BMI-1 and MUC1-C.
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spelling pubmed-57464022018-01-03 MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells Koh, Hyebin Park, Hyeri Chandimali, Nisansala Huynh, Do Luong Zhang, Jiao Jiao Ghosh, Mrinmoy Gera, Meeta Kim, Nameun Bak, Yesol Yoon, Do-Young Park, Yang Ho Kwon, Taeho Jeong, Dong Kee Oncotarget Research Paper The existence of cancer stem cells (CSCs) is the main reason for failure of cancer treatment caused by drug resistance. Therefore, eradicating cancers by targeting CSCs remains a significant challenge. In the present study, because of the important role of BMI-1 proto-oncogene, polycomb ring finger (BMI-1) and C-terminal Mucin1 (MUC1-C) in tumor growth and maintenance of CSCs, we aimed to confirm that microRNA miR-128, as an inhibitor of BMI-1 and MUC1-C, could effectively suppress paclitaxel (PTX)-resistant lung cancer stem cells. We showed that CSCs have significantly higher expression levels of BMI-1, MUC1-C, stemness proteins, signaling factors, and higher malignancy compared with normal tumor cells. After transfection with miR-128, the BMI-1 and MUC1-C levels in CSCs were suppressed. When miR-128 was stably expressed in PTX-resistant lung cancer stem cells, the cells showed decreased proliferation, metastasis, self-renewal, migration, invasive ability, clonogenicity, and tumorigenicity in vitro and in vivo and increased apoptosis compared with miR-NC (negative control) CSCs. Furthermore, miR-128 effectively decreased the levels of β-catenin and intracellular signaling pathway-related factors in CSCs. MiR-128 also decreased the luciferase activity of MUC1 reporter constructs and reduced the levels of transmembrane MUC1-C and BMI-1. These results suggested miR-128 as an attractive therapeutic strategy for PTX-resistant lung cancer via inhibition of BMI-1 and MUC1-C. Impact Journals LLC 2017-11-30 /pmc/articles/PMC5746402/ /pubmed/29299167 http://dx.doi.org/10.18632/oncotarget.22818 Text en Copyright: © 2017 Koh et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Koh, Hyebin
Park, Hyeri
Chandimali, Nisansala
Huynh, Do Luong
Zhang, Jiao Jiao
Ghosh, Mrinmoy
Gera, Meeta
Kim, Nameun
Bak, Yesol
Yoon, Do-Young
Park, Yang Ho
Kwon, Taeho
Jeong, Dong Kee
MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells
title MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells
title_full MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells
title_fullStr MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells
title_full_unstemmed MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells
title_short MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells
title_sort microrna-128 suppresses paclitaxel-resistant lung cancer by inhibiting muc1-c and bmi-1 in cancer stem cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746402/
https://www.ncbi.nlm.nih.gov/pubmed/29299167
http://dx.doi.org/10.18632/oncotarget.22818
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