TY - JOUR
T1 - The microRNA miR-181c enhances chemosensitivity and reduces chemoresistance in breast cancer cells via down-regulating osteopontin
AU - Han, Baojuan
AU - Huang, Jian
AU - Han, Yunfeng
AU - Hao, Jie
AU - Wu, Xueya
AU - Song, Hongtao
AU - Chen, Xuesong
AU - Shen, Qiang
AU - Dong, Xiaoqun
AU - Pang, Hui
AU - Cai, Li
N1 - Publisher Copyright:
© 2018
PY - 2019/3/15
Y1 - 2019/3/15
N2 - Acquired resistance to chemotherapy is a frequent challenge in cancer care and one of the leading causes for failing breast cancer therapies. There is accumulative clinical and experimental evidence indicating that microRNAs (miRNAs) play a crucial role in developing therapeutic resistance in cancer cells. We aimed to explore key miRNAs and associated mechanisms by which breast cancer develops chemoresistance. In this study, we found that a particular miRNA species, miR-181c, was significantly low-expressed in breast cancer cell line MCF-7 which developed chemoresistance towards doxorubicin (Adriamycin, ADR, subclone renamed as MCF-7/ADR) than in the wild-type MCF-7 cells. Induced overexpression of miR-181c significantly inhibited cell proliferation, reversed the chemoresistance towards doxorubicin, and reduced the growth of resistant breast cancer xenograft tumors in vitro and in vivo. Using a bioinformatics approach, we also identified osteopontin (OPN) as a direct target of miR-181c. In contrast to low miR-181c expression in MCF-7/ADR cells, OPN showed a reversely high expression in resistant MCF-7/ADR cells. Our results suggest that miR-181c may regulate chemosensitivity and chemoresistance by downregulating OPN, resulting in enhanced p53-dependent transactivation and apoptosis in resistant breast cancer cells. This study provides new insights to develop effective interventions for cancer patients with acquired resistance to chemotherapy.
AB - Acquired resistance to chemotherapy is a frequent challenge in cancer care and one of the leading causes for failing breast cancer therapies. There is accumulative clinical and experimental evidence indicating that microRNAs (miRNAs) play a crucial role in developing therapeutic resistance in cancer cells. We aimed to explore key miRNAs and associated mechanisms by which breast cancer develops chemoresistance. In this study, we found that a particular miRNA species, miR-181c, was significantly low-expressed in breast cancer cell line MCF-7 which developed chemoresistance towards doxorubicin (Adriamycin, ADR, subclone renamed as MCF-7/ADR) than in the wild-type MCF-7 cells. Induced overexpression of miR-181c significantly inhibited cell proliferation, reversed the chemoresistance towards doxorubicin, and reduced the growth of resistant breast cancer xenograft tumors in vitro and in vivo. Using a bioinformatics approach, we also identified osteopontin (OPN) as a direct target of miR-181c. In contrast to low miR-181c expression in MCF-7/ADR cells, OPN showed a reversely high expression in resistant MCF-7/ADR cells. Our results suggest that miR-181c may regulate chemosensitivity and chemoresistance by downregulating OPN, resulting in enhanced p53-dependent transactivation and apoptosis in resistant breast cancer cells. This study provides new insights to develop effective interventions for cancer patients with acquired resistance to chemotherapy.
KW - Breast cancer
KW - Chemoresistance
KW - OPN
KW - miR-181c
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U2 - 10.1016/j.ijbiomac.2018.12.075
DO - 10.1016/j.ijbiomac.2018.12.075
M3 - Article
C2 - 30537505
AN - SCOPUS:85058955225
SN - 0141-8130
VL - 125
SP - 544
EP - 556
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
ER -