Downregulation of galectin-3 causes a decrease in uPAR levels and inhibits the proliferation, migration and invasion of hepatocellular carcinoma cells

Zheng,Datong; Hu,Zhenzhen; He,Fan; Gao,Caijie; Xu,Lijian; Zou,Han; Wu,Zhiwei; Jiang,Xiuqin; Wang,Jianjun

doi:10.3892/or.2014.3170

Downregulation of galectin-3 causes a decrease in uPAR levels and inhibits the proliferation, migration and invasion of hepatocellular carcinoma cells

Authors:
- Datong Zheng
- Zhenzhen Hu
- Fan He
- Caijie Gao
- Lijian Xu
- Han Zou
- Zhiwei Wu
- Xiuqin Jiang
- Jianjun Wang
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Affiliations: 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, Research Center, The Second Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China, Immunology and Reproductive Biology Laboratory and Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu 210093, P.R. China
Published online on: May 8, 2014 https://doi.org/10.3892/or.2014.3170
Pages: 411-418

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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.

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