miR-222 confers the resistance of breast cancer cells to Adriamycin through suppression of p27(kip1) expression.
Adriamycin (Adr) is a potent chemotherapeutic agent for chemotherapy of breast cancer patients. Despite impressive initial clinical responses, some developed drug resistance to Adr-based therapy and the mechanisms underlying breast cancer cells resistance to Adr are not well known. In our previous study, in vitro, we verified that miR-222 was upregulated in Adr-resistant breast cancer cells (MCF-7/Adr) compared with the sensitive parental cells (MCF-7/S). Here, miR-222 inhibitors or mimics were transfected into MCF-7 cell lines. RT-qPCR and western blot were used to detect the expression of p27(kip1). Immunofluorescence showed that miR-222 altered the subcellular location of p27(kip1) in nucleus. MTT was employed to verify the sensitivity of breast cancer cell lines to Adr. Flow cytometry showed the apoptosis and cell cycles of the cells after adding Adr. The results showed that downregulation of miR-222 in MCF-7/Adr increased sensitivity to Adr and Adr-induced apoptosis, and arrested the cells in G1 phase, accompanied by more expressions of p27(kip1), especially in nucleus. Furthermore, overexpressed miR-222 in MCF-7/S had the inverse results. Taken together, the results found that miR-222 induced Adr-resistance at least in part via suppressing p27(kip1) expression and altering its subcellular localization, and miR-222 inhibitors could reverse Adr-resistance of breast cancer cells. These results disclosed that the future holds much promise for the targeted therapeutic in the treatment of Adr-resistant breast cancer.
The First Clinical School of Nanjing Medical University, Nanjing 210009, China; Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China.
Dan-Dan
DD
Wang
The Forth Clinical School of Nanjing Medical University, Nanjing 210009, China; Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China.
Jian
J
Li
The Forth Clinical School of Nanjing Medical University, Nanjing 210009, China.
Huan-Huan
HH
Sha
The Forth Clinical School of Nanjing Medical University, Nanjing 210009, China; Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China.
Xiu
X
Chen
The Forth Clinical School of Nanjing Medical University, Nanjing 210009, China; Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China.
Su-Jin
SJ
Yang
The Forth Clinical School of Nanjing Medical University, Nanjing 210009, China; Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China.
Hong-Yu
HY
Shen
Center of Clinical Laboratory, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China.
Shan-Liang
SL
Zhong
Center of Clinical Laboratory, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China. Electronic address: jhzhaojsccl@126.com.
Jian-Hua
JH
Zhao
Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Baiziting 42, Nanjing 210009, China; Department of General Surgery, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, P.R. China. Electronic address: jinhangtangjsch@163.com.
Jin-Hai
JH
Tang
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics* / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020320:Oligoribonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D000903:Antibiotics, Antineoplastic; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004317:Doxorubicin; D035683:MicroRNAs; D020320:Oligoribonucleotides, Antisense; C525710:MIR222, human
Adriamycin; Breast cancer; Drug resistance; miR-222; p27(kip1)