tailieunhanh - Báo cáo khoa học: MicroRNA-23b mediates urokinase and c-met downmodulation and a decreased migration of human hepatocellular carcinoma cells

Urokinase-type plasminogen activator (uPA) and c-met play a major role in cancer invasion and metastasis. Evidence has suggested that uPA and c-met overexpression may be coordinated in human hepatocellular carci-noma (HCC). In the present study, to understand whether the expression of these genes might be coregulated by specific microRNAs (miRs) in human cells, we predicted thatHomo sapiensmicroRNA-23b could recog-nize two sites in the 3¢-UTR of uPA and four sites in the c-met 3¢-UTR by the algorithm pictar. . | MicroRNA-23b mediates urokinase and c-met downmodulation and a decreased migration of human hepatocellular carcinoma cells Alessandro Salvi1 Cristiano Sabelli1 Silvia Moncini2 Marco Venturin2 Bruna Arici1 Paola Riva2 Nazario Portolani3 Stefano M. Giulini3 Giuseppina De Petro1 and Sergio Barlati1 1 Division of Biology and Genetics Department of BiomedicalSciences and Biotechnology IDET Centre of Excellence University of Brescia Italy 2 Department of Biology and Genetics MedicalFaculty University of Milan Italy 3 Department of Medicaland SurgicalSciences University of Brescia Italy Keywords c-met hepatocellular carcinoma cells microRNA-23b urokinase Correspondence G. De Petro Department of Biomedical Sciences and Biotechnology Division of Biology and Genetics University of Brescia Viale Europa n. 11 25123 Brescia Italy Fax 39 30 3701157 Tel 39 30 3717 264 241 E-mail depetro@ Received 19 December 2008 revised 18 March 2009 accepted 19 March 2009 doi Urokinase-type plasminogen activator uPA and c-met play a major role in cancer invasion and metastasis. Evidence has suggested that uPA and c-met overexpression may be coordinated in human hepatocellular carcinoma HCC . In the present study to understand whether the expression of these genes might be coregulated by specific microRNAs miRs in human cells we predicted that Homo sapiens microRNA-23b could recognize two sites in the 3 -UTR of uPA and four sites in the c-met 3 -UTR by the algorithm PICTAR. The miR-23b expression analysis in human tumor and normal cells revealed an inverse trend with uPA and c-met expression indicating that uPA and c-met negative regulation might depend on miR-23b expression. Transfection of miR-23b molecules in HCC cells SKHep1C3 led to inhibition of protein expression of the target genes and caused a decrease in cell migration and proliferation capabilities. Furthermore anti-miR-23b transfection in human normal AB2 dermal fibroblasts upregulated the