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A Journal on Internal Medicine
Indexed/Abstracted in: Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,236
Minerva Medica 2015 August;106(4):193-202
microRNA-200c overexpression plays an inhibitory role in human pancreatic cancer stem cells by regulating epithelial-mesenchymal transition
Ma C., Ding Y. C., Yu W., Wang Q., Meng B., Huang T. ✉
Department of Hepatopancreatobiliary Surgery, The Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, China
AIM: Cancer stem cells (CSCs) are believed to be the ‘seed cell’ in cancer recurrence and metastasis. MicroRNAs (miRNAs) have emerged as potential therapeutic candidates due to their ability to regulate the epithelial-mesenchymal transition (EMT). The goal of this study was to investigate the effect of miRNA-200c (miR-200c) on the EMT, tumorigenesis, 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 relative mRNA expression levels of miR-200c and EMT-associated phenotypes. Transfection of miR-200c mimic into PCSCs was performed to establish miR-200c overexpressed cells. The assays of colony forming, cellular invasion and survival in vitro and tumor progression in vivo were performed.
RESULTS: Expression of miR-200c was significantly reduced in PCSCs compared with PANC-1 cells. However, the stable over expression of the miR-200c in the PCSCs resulted in a significant down-regulation of zinc-finger E-box binding homeobox 1 (ZEB1) and the Vimentin expression, an upregulation of the E-cadherin expression as well as a decrease of colony forming, chemoresistance and invasion in vitro and xenograft growth in vivo in nude mice by inhibition of the EMT.
CONCLUSION: Our study demonstrated that miR-200c may become a new therapeutic target for gene therapy in patients suffered from pancreatic cancer.