MicroRNA-200c overexpression inhibits chemoresistance, invasion and colony formation of human pancreatic cancer stem cells.
BACKGROUND
Cancer stem cells (CSCs) are believed to be 'seed cell' in cancer recurrence and metastasis. MicroRNAs (miRNAs) have emerged as potential therapeutic candidates due to their ability to regulate multiple targets involved in tumor progression and chemoresistance. The goal of this study was to investigate the role of miRNA-200c (miR-200c) in regulating colony formation, invasion and chemoresistance of human pancreatic cancer stem cells (PCSCs).


METHODS
PCSCs with CD24(+)CD44(+)ESA(+) as the marker was sorted from PANC-1 cell line by fluorescence activated cell sorter (FACS). Quantitative real-time PCR (qRT-PCR) assay was used to detect the expression of miR-200c in PCSCs and PANC-1 cells. Transfection of miR-200c mimic into PCSCs was performed to establish miR-200c over-expressed cells. The effects of overexpressing miR-200c on PCSCs were examined by cell colony forming, invasion and survival assays in vitro.


RESULTS
Our data showed that CD24(+)CD44(+)ESA(+) PCSCs (0.5%) were isolated from PANC-1 cells. Expression of miR-200c was significantly reduced in PCSCs compared with PANC-1 cells. In addition, the capability of colony formation, invasion and chemoresistance were markedly increased in PCSCs than that in PANC-1 cells. Adverse results were obtained in miR-200c overexpressing PCSCs transfected with miR-200c mimic.


CONCLUSIONS
Our study demonstrated that miR-200c overexpression could decrease colony formation, invasion and chemoresistance of PCSCs. It may become a new therapeutic target for gene therapy in patients suffered from pancreatic cancer.
Department of Hepatopancreatobiliary Surgery, The Affiliated Tumor Hospital of Zhengzhou University Zhengzhou 450008, China.
Chao
C
Ma
Department of Hepatopancreatobiliary Surgery, The Affiliated Tumor Hospital of Zhengzhou University Zhengzhou 450008, China.
Tao
T
Huang
Department of Hepatopancreatobiliary Surgery, The Affiliated Tumor Hospital of Zhengzhou University Zhengzhou 450008, China.
Yue-Chao
YC
Ding
Department of Hepatopancreatobiliary Surgery, The Affiliated Tumor Hospital of Zhengzhou University Zhengzhou 450008, China.
Wei
W
Yu
Department of Hepatopancreatobiliary Surgery, The Affiliated Tumor Hospital of Zhengzhou University Zhengzhou 450008, China.
Qian
Q
Wang
Department of Hepatopancreatobiliary Surgery, The Affiliated Tumor Hospital of Zhengzhou University Zhengzhou 450008, China.
Bo
B
Meng
Department of Medical Gastroenterology, The Affiliated Tumor Hospital of Zhengzhou University Zhengzhou 450008, China.
Su-Xia
SX
Luo
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D014162:Transfection; D015854:Up-Regulation; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D003841:Deoxycytidine; D000093542:Gemcitabine
Pancreatic cancer; cancer stem cells; chemoresistance; invasion; microRNA-200c