The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS

• Published in: Carcinogenesis (New York) 2010-10, Vol.31 (10), p.1726-1733
• Main Authors: Zhao, Wu-Gan, Yu, Shuang-Ni, Lu, Zhao-Hui, Ma, Yi-Hui, Gu, Yu-Mei, Chen, Jie
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - pathology; Animals; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinoma, Pancreatic Ductal - pathology; Cell Line, Tumor; Gastroenterology. Liver. Pancreas. Abdomen; Genes, Tumor Suppressor; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Mice; Mice, Inbred BALB C; MicroRNAs - analysis; MicroRNAs - physiology; Pancreatic Neoplasms - pathology; Proto-Oncogene Proteins - analysis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - analysis; ras Proteins - genetics; Tumors
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgq160

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.