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Biochem Biophys Res Commun ; 435(3): 466-71, 2013 Jun 07.
Article in English | MEDLINE | ID: mdl-23673296

ABSTRACT

MicroRNAs (miRNAs) play important roles in the development of various cancers. MiRNA-497 functions as a tumor-suppressor that is downregulated in several malignancies; however, its role in non-small cell lung cancer (NSCLC) has not been examined in detail. Here, we showed that miR-497 is downregulated in NSCLC tumors and cell lines and its ectopic expression significantly inhibits cell proliferation and colony formation. Integrated analysis identified HDGF as a downstream target of miR-497, and the downregulation of HDGF by miR-497 overexpression confirmed their association. Rescue experiments showed that the inhibitory effect of miR-497 on cell proliferation and colony formation is predominantly mediated by the modulation of HDGF levels. Furthermore, tumor samples from NSCLC patients showed an inverse relationship between miR-497 and HDGF levels, and ectopic expression of miR-497 significantly inhibited tumor growth and angiogenesis in a SCID mouse xenograft model. Our results suggest that miR-497 may serve as a biomarker in NSCLC, and the modulation of its activity may represent a novel therapeutic strategy for the treatment of NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Down-Regulation/genetics , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Lung Neoplasms/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/blood supply , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line , Cell Line, Tumor , Disease Models, Animal , Gene Targeting/methods , Humans , Lung Neoplasms/blood supply , Lung Neoplasms/pathology , Mice , Mice, SCID , Neovascularization, Pathologic/genetics , Transplantation, Heterologous
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