Knockdown of Dicer in MCF-7 human breast carcinoma cells results in G1 arrest and increased sensitivity to cisplatin.
Aberrant expression of microRNAs (miRNAs) in various human cancers suggests a role for miRNAs in tumorigenesis. Dicer is an essential component of the miRNA machinery, which mediates the processing of miRNAs. However, little is known about the role of Dicer in tumor proliferation and drug resistance. In this study, we found that knockdown of Dicer by siRNA led to significant G1 arrest and increased sensitivity to the DNA damaging agent, cisplatin, in breast cancer cell line MCF-7. Moreover, we found down-regulation of miR-21, a well-recognized miRNA frequently involved in a wide variety of cancers and up-regulation of cell cycle-dependent kinase inhibitor (CKI) p21 and p27. These data demonstrate that knockdown of Dicer inhibits human breast carcinoma cell growth and suggests a promising combination of anti-Dicer strategy and traditional chemotherapy to improve cancer treatment efficiency.
Bu
Ye
Y
Center of Tissue Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, PR China.
Lu
Chunhua
C
Bian
Chunjing
C
Wang
Jinghua
J
Li
Jing
J
Zhang
Bin
B
Li
Zhenya
Z
Brewer
Gary
G
Zhao
Robert Chunhua
RC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D016193:G1 Phase / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D000970:Antineoplastic Agents; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D043244:Ribonuclease III; D002945:Cisplatin