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Down-regulation of Gli-1 inhibits hepatocellular carcinoma cell migration and invasion

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Abstract

Glioma-associated oncogene homolog-1 (Gli-1) is considered a marker of Hedgehog pathway activation and is associated with the progression of several cancers. We have previously reported that Gli-1 was correlated with invasion and metastasis in hepatocellular carcinoma (HCC). However, the exact roles and mechanisms of Gli-1 in HCC invasion are unclear. In this study, we found that small interfering RNA mediated down-regulation of Gli-1 expression significantly suppressed adhesion, motility, migration, and invasion of both SMMC-7721 and SK-Hep1 cells. Furthermore, down-regulation of Gli-1 significantly reduced expressions and activities of both matrix metalloproteinase (MMP)-2 and MMP-9. In addition, we found that down-regulation of Gli-1 resulted in up-regulation of E-cadherin and concomitant down-regulation of Snail and Vimentin, consistent with inhibition of epithelial-mesenchymal transition (EMT). Taken together, our results suggest that down-regulation of Gli-1 suppresses HCC cell migration and invasion likely through inhibiting expressions and activations of MMP-2, 9 and blocking EMT.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81201930, 81101862, 81172079); Research Fund for the Doctoral Program of Higher Education of China (20124423120006); Natural Science Foundation of Guangdong Province (S2012040006803, S2013010016831); Key Project of Guangzhou Municipal Science & Technology Planning (2011J4100053), Doctoral Research Foundation of Guangzhou Medical University (2010C23), and Foundation for Youth Teachers by Sun Yat-Sen University(11ykpy16).

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Authors and Affiliations

  1. Department of Gastrointesinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China

    Jing-Song Chen, Jiong-Qiang Huang, Jian Lei, Ju-Tao Feng & Qin Liu

  2. Department of Gynaecology and Obstetrics, The Second People’s Hospital of Liwan District, Guangzhou, 510160, People’s Republic of China

    Hua-Shu Li

  3. Surgical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Long-Juan Zhang & Xiao-Hui Huang

  4. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Xi-Lin Chen & Qian Wang

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  1. Jing-Song Chen
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Correspondence to Xiao-Hui Huang.

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Chen, JS., Li, HS., Huang, JQ. et al. Down-regulation of Gli-1 inhibits hepatocellular carcinoma cell migration and invasion. Mol Cell Biochem 393, 283–291 (2014). https://doi.org/10.1007/s11010-014-2071-x

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