4.5 Article

MicroRNA-20a Overexpression Inhibited Proliferation and Metastasis of Pancreatic Carcinoma Cells

期刊

HUMAN GENE THERAPY
卷 21, 期 12, 页码 1723-1734

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MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2010.061

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资金

  1. National Key Basic Research Program of China [2010CB912201]
  2. National High Technology Research and Development Program of China [2007AA021202, 2007AA021203, 2010CB529904]
  3. Science Research Project of Eleventh Five-Year Plan [2008ZX09101-051]
  4. National Science Fund of China [30973448]

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The aim of this study was to investigate the effect of microRNA-20a on pancreatic carcinoma cell proliferation and invasion and to find a new effective treatment strategy for pancreatic carcinoma. MicroRNA-20a expression was determined in 10 matched normal pancreatic tissues and pancreatic carcinoma by in situ hybridization. Quantitative real-time RT-PCR was used to evaluate the expression of microRNA-20a in two pancreatic carcinoma cell lines (BxPC-3 and Panc-1) and immortal human pancreatic duct epithelial cell line H6C7. Proliferation and invasion capacity were analyzed for the cells with lentivirus-mediated overexpression of microRNA-20a both in vitro and in vivo. In addition, the regulation of signal transducer and activator of transcription proteins 3 (Stat3) by microRNA-20a was determined to elucidate the underlying mechanisms. The pancreatic cancer cell lines (Panc-1 and BxPC-3) stably overexpressing microRNA-20a showed reduced proliferation and invasion capacity in vitro and in vivo, compared with parental cells or cells transfected with a control vector. Furthermore, we found that microRNA-20a negatively regulated Stat3 protein expression in a dose-dependent manner without changing the Stat3mRNA level and decreased the activity of a luciferase reporter construct containing the Stat3 3'-untranslated region. These results show that microRNA-20a regulates Stat3 at the post-transcriptional level, resulting in inhibition of cell proliferation and invasion of pancreatic carcinoma. It may open a new perspective for the development of effective gene therapy for pancreatic carcinoma.

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