title: Downregulation of galectin-3 causes a decrease in uPAR levels and inhibits the proliferation, migration and invasion of hepatocellular carcinoma cells.
abstract: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. Galectin-3 (Gal-3), a multifunctional β-galactoside-binding protein, is highly expressed and associated with the prognosis of HCC. However, the functions of Gal-3 in HCC cells are not fully understood. To address the function of Gal-3 in HCC cells, we used small interfering RNA (siRNA) to knock down Gal-3 expression in HepG2, an HCC cell line. We found that in vitro the silencing of Gal-3 decreased the proliferative activity, colony formation ability, migratory and invasive potential of HepG2 cells. The silencing of Gal-3 significantly decreased the mRNA and protein levels of urokinase-type plasminogen activator receptor (uPAR) as well as uPAR's downstream signaling transduction pathway, including phosphorylation of AKT. Furthermore, the downregulation of Gal-3 by siRNA resulted in significantly decreased activity of the MEK/ERK signaling pathway, and the treatment of HepG2 cells with MEK/ERK inhibitor U0126 significantly reduced the mRNA and protein levels of uPAR. Taken together, our results suggest that Gal-3 modulates uPAR expression via the MEK/ERK pathway, and that Gal-3 may be a potential therapeutic target for the treatment of HCC.
authors.affiliation: Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Datong
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Research Center, The Second Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Research Center, The Second Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: He
authors.affiliation: Research Center, The Second Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.
authors.forename: Caijie
authors.initials: C
authors.lastname: Gao
authors.affiliation: Research Center, The Second Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Xu
authors.affiliation: Research Center, The Second Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Zou
authors.affiliation: Immunology and Reproductive Biology Laboratory and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Research Center, The Second Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210093, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wang
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D037502:Galectin 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D009570:Nitriles / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002070:Butadienes; D037502:Galectin 3; D009570:Nitriles; D034741:RNA, Small Interfering; D055293:Receptors, Urokinase Plasminogen Activator; C113580:U 0126