MiR-489 regulates chemoresistance in breast cancer via epithelial mesenchymal transition pathway.
To investigate the role of microRNAs in the development of chemoresistance and related epithelial-mesenchymal transition (EMT), we examined the effect of miR-489 in adriamycin (ADM)-resistant human breast cancer cells (MCF-7/ADM). MiR-489 was significantly suppressed in MCF-7/ADM cells compared with chemosensitive parental control MCF-7/WT cells. Forced-expression of miR-489 reversed chemoresistance. Furthermore, Smad3 was identified as the target of miR-489 and is highly expressed in MCF-7/ADM cells. Forced expression of miR-489 both inhibited Smad3 expression and Smad3 related EMT properties. Finally, the interactions between Smad3, miR-489 and EMT were confirmed in chemoresistant tumor xenografts and clinical samples, indicating their potential implication for treatment of chemoresistance.
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
Li
L
Jiang
National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
Dongxu
D
He
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
Dantong
D
Yang
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
Zhen
Z
Chen
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
Qiongxi
Q
Pan
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
Aiqin
A
Mao
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
Yanfei
Y
Cai
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
Xiyuan
X
Li
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
Hui
H
Xing
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
Mei
M
Shi
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
Yun
Y
Chen
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
Iain C
IC
Bruce
Affiliated Hospital, Jiangnan University, Wuxi, China.
Teng
T
Wang
Affiliated Hospital, Jiangnan University, Wuxi, China.
Linfang
L
Jin
Affiliated Hospital, Jiangnan University, Wuxi, China.
Xiaowei
X
Qi
Affiliated Hospital, Jiangnan University, Wuxi, China.
Dong
D
Hua
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China. Electronic address: jinjian31@126.com.
Jian
J
Jin
School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China. Electronic address: maxin@jiangnan.edu.cn.
Xin
X
Ma
D020413:3' Untranslated Regions; D000818:Animals; D018943:Anthracyclines / Q000494:pharmacology / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D020360:Neoadjuvant Therapy; D034622:RNA Interference; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D020413:3' Untranslated Regions; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; C552418:MIRN489 microRNA, human; D035683:MicroRNAs; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D043823:Taxoids; D004317:Doxorubicin
Breast cancer; Chemoresistance; Epithelial mesenchymal transition; microRNAs