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The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS.
- Source :
-
Carcinogenesis . Oct2010, Vol. 31 Issue 10, p1726-1733. 8p. 1 Diagram, 2 Charts, 3 Graphs. - Publication Year :
- 2010
-
Abstract
- Aberrantly expressed microRNA (miRNA) is frequently associated with a variety of cancers, including pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the expression and possible role of miR-217 in PDAC. Data obtained by locked nucleic acid in situ hybridization and real-time quantitative polymerase chain reaction showed that miR-217 was downregulated in 76.2% (16/21) of PDAC tissues and in all tested PDAC cell lines when compared with the corresponding normal pancreatic tissue. Overexpression of miR-217 in PDAC cells inhibited tumor cell growth and anchorage-independent colony formation and miR-217 decreased tumor cell growth in nude mouse xenografts in vivo. Using in silico predictions, KRAS was defined as a potential direct target of miR-217. Data from the dual-luciferase reporter gene assay showed that KRAS was a direct target of miR-217. Upregulation of miR-217 could decrease KRAS protein levels and reduce the constitutive phosphorylation of downstream AKT. Downregulation of miR-217 expression in PDAC cells could increase cell anchorage-independent colony formation and KRAS protein levels. Furthermore, miR-217 expression was observed to be negatively correlated with KRAS protein expression in PDAC cell lines. We conclude that the frequently downregulated miR-217 can regulate KRAS and function as a tumor suppressor in PDAC. Therefore, miR-217 may serve as a useful therapeutic agent for miRNA-based PDAC therapy. [ABSTRACT FROM PUBLISHER]
- Subjects :
- *CANCER genetics
*ADENOCARCINOMA
*GENE expression
*CANCER cells
*PANCREAS
Subjects
Details
- Language :
- English
- ISSN :
- 01433334
- Volume :
- 31
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 54400231
- Full Text :
- https://doi.org/10.1093/carcin/bgq160