MicroRNA-320a promotes 5-FU resistance in human pancreatic cancer cells.
The drug-resistance of pancreatic cancer cells results in poor therapeutic effect. To predict the therapeutic effect of the chemotherapy drugs to specific patients and to reverse the resistance of pancreatic cancer cells are critical for chemotherapy of pancreatic cancer. MicroRNAs (miRNAs) have been reported to play important roles in the genesis of drug-resistance of various cancer types. There are also many advantages of miRNAs in diagnosis and therapy of disease. Although several miRNAs regulating 5-Fluorouracil (5-FU) resistance in human pancreatic cancer have been reported, the detailed molecular mechanism remains to be determined. In this study, we found that miR-320a was significantly up-regulated in 5-FU resistant pancreatic cancer cells. Over-expression of miR-320a strongly contributed to pathogenesis of pancreatic cancer, which was represented by the increased proliferation, invasion, metastasis, drug-resistance characteristics and the epithelial-to-mesenchymal transition. Furthermore, we demonstrated that miR-320a was able to bind to 3'UTR of PDCD4 mRNA, and mediated its down-regulation in 5-FU resistance of human pancreatic cancer cells. Whereas restoration of PDCD4 expression could partially attenuate the function of miR-320a in pancreatic cancer. Taken together, our study demonstrated that miR-320a played important role in regulating 5-FU resistance by targeting PDCD4 and might be developed as new therapeutic target for pancreatic cancer.
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science &Peking Union Medical College, Beijing 100730, PR China.
Weibin
W
Wang
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, PR China.|Institute of Molecular Medicine, Medical School, Henan University, KaiFeng, 475000, PR China.
Lijun
L
Zhao
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, PR China.|Institute of Molecular Medicine, Medical School, Henan University, KaiFeng, 475000, PR China.
Xueju
X
Wei
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, PR China.|Institute of Molecular Medicine, Medical School, Henan University, KaiFeng, 475000, PR China.
Lanlan
L
Wang
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, PR China.
Siqi
S
Liu
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science &Peking Union Medical College, Beijing 100730, PR China.
Yu
Y
Yang
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, PR China.
Fang
F
Wang
Institute of Molecular Medicine, Medical School, Henan University, KaiFeng, 475000, PR China.
Guotao
G
Sun
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, PR China.
Junwu
J
Zhang
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, PR China.
Yanni
Y
Ma
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science &Peking Union Medical College, Beijing 100730, PR China.
Yupei
Y
Zhao
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, PR China.
Jia
J
Yu
D020413:3' Untranslated Regions; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D005472:Fluorouracil