miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1
MicroRNAs (miRNAs) family, which is involved in cancer development, proliferation, apoptosis, and drug resistance, is a group of noncoding RNAs that modulate the expression of oncogenes and antioncogenes. Doxorubicin is an active cytotoxic agent for breast cancer treatment, but the acquisition of do...
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doaj-02c0fb67ab9341948a7e34f1c8be849e2020-11-24T22:36:42ZengHindawi LimitedBioMed Research International2314-61332314-61412015-01-01201510.1155/2015/373574373574miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1Jingpei Long0Zhiwei Ji1Kai Jiang2Zhaoyang Wang3Guanmin Meng4Department of Surgery, The Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaSchool of Electronics and Information Engineering, Tongji University, Shanghai 201804, ChinaDepartment of Clinical Laboratory, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou 310012, ChinaDepartment of Ophthalmology, Xinhua Hospital, School of Medicine, Jiaotong University, Shanghai 200092, ChinaDepartment of Clinical Laboratory, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou 310012, ChinaMicroRNAs (miRNAs) family, which is involved in cancer development, proliferation, apoptosis, and drug resistance, is a group of noncoding RNAs that modulate the expression of oncogenes and antioncogenes. Doxorubicin is an active cytotoxic agent for breast cancer treatment, but the acquisition of doxorubicin resistance is a common and critical limitation to cancer therapy. The aim of this study was to investigate whether miR-193b mediated the resistance of breast cancer cells to doxorubicin by targeting myeloid cell leukemia-1 (MCL-1). In this study, we found that miR-193b levels were significantly lower in doxorubicin-resistant MCF-7 (MCF-7/DOXR) cells than in the parental MCF-7 cells. We observed that exogenous miR-193b significantly suppressed the ability of MCF-7/DOXR cells to resist doxorubicin. It demonstrated that miR-193b directly targeted MCL-1 3′-UTR (3′-Untranslated Regions). Further studies indicated that miR-193b sensitized MCF-7/DOXR cells to doxorubicin through a mechanism involving the downregulation of MCL-1. Together, our findings provide evidence that the modulation of miR-193b may represent a novel therapeutic target for the treatment of breast cancer.http://dx.doi.org/10.1155/2015/373574 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jingpei Long Zhiwei Ji Kai Jiang Zhaoyang Wang Guanmin Meng |
spellingShingle |
Jingpei Long Zhiwei Ji Kai Jiang Zhaoyang Wang Guanmin Meng miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1 BioMed Research International |
author_facet |
Jingpei Long Zhiwei Ji Kai Jiang Zhaoyang Wang Guanmin Meng |
author_sort |
Jingpei Long |
title |
miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1 |
title_short |
miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1 |
title_full |
miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1 |
title_fullStr |
miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1 |
title_full_unstemmed |
miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1 |
title_sort |
mir-193b modulates resistance to doxorubicin in human breast cancer cells by downregulating mcl-1 |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2015-01-01 |
description |
MicroRNAs (miRNAs) family, which is involved in cancer development, proliferation, apoptosis, and drug resistance, is a group of noncoding RNAs that modulate the expression of oncogenes and antioncogenes. Doxorubicin is an active cytotoxic agent for breast cancer treatment, but the acquisition of doxorubicin resistance is a common and critical limitation to cancer therapy. The aim of this study was to investigate whether miR-193b mediated the resistance of breast cancer cells to doxorubicin by targeting myeloid cell leukemia-1 (MCL-1). In this study, we found that miR-193b levels were significantly lower in doxorubicin-resistant MCF-7 (MCF-7/DOXR) cells than in the parental MCF-7 cells. We observed that exogenous miR-193b significantly suppressed the ability of MCF-7/DOXR cells to resist doxorubicin. It demonstrated that miR-193b directly targeted MCL-1 3′-UTR (3′-Untranslated Regions). Further studies indicated that miR-193b sensitized MCF-7/DOXR cells to doxorubicin through a mechanism involving the downregulation of MCL-1. Together, our findings provide evidence that the modulation of miR-193b may represent a novel therapeutic target for the treatment of breast cancer. |
url |
http://dx.doi.org/10.1155/2015/373574 |
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