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Stealth siRNA against CD147 inhibits hepatocellular carcinoma cell metastatic properties

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Abstract

CD147 plays a critical role in the invasive and metastatic activity of hepatocellular carcinoma (HCC) cells by stimulating the surrounding fibroblasts to secrete matrix metalloproteinases (MMPs). Tumor cells adhesion to extracellular matrix (ECM) proteins is the first step to the tumor metastasis. MMPs degrade the ECM to promote tumor metastasis. The aim of this research was to investigate the inhibitory effects of stealth small interfering RNA (siRNA) against CD147 on HCC cell line (SMMC-7721) metastatic properties including invasion, adhesion to ECM, gelatinase production, focal adhesion kinase (FAK) and vinculin expression. Flow cytometry (FCM) and western blot assays were employed to detect the transfection efficiency of the stealth siRNA against CD147. Invasion assays and gelatin zymography were also used to detect the effects of stealth siRNA against CD147 on SMMC-7721 cells’ invasion and gelatinase production. The effects of stealth siRNA against CD147 on FAK and vinculiln expression in SMMC-7721 cells were also detected by western blot. The results showed that stealth siRNA against CD147 inhibited SMMC-7721 invasion, adhesion to ECM proteins, MMP-2 production, and FAK and vinculin expression. These findings indicate that CD147 is required for tumor cell invasion and adhesion. Perturbation of CD147 expression may have potential therapeutic uses in the prevention of MMP-2-dependent tumor invasion.

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Abbreviations

dsRNA:

double-stranded RNA

ECM:

extracellular matrix

EMMPRIN:

extracellular matrix metalloproteinase inducer

ERK1/2:

extracellular signal-regulated kinase 1/2

FAK:

focal adhesion kinase

FCM:

flow cytometry

FN:

fibronectin

GAPDH:

glyceraldehyde 3-phosphate dehydrogenase

HCC:

hepatocellular carcinoma

LN:

laminin

MEK1:

mitogen-activated protein kinase kinase 1

MMPs:

matrix metalloproteinases

siRNA:

small interfering RNA

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Authors and Affiliations

  1. Institute of Special Environmental Biophysics, Key Laboratory for Space Biosciences & Biotechnology, Faculty of Life Sciences, Northwestern Polytechnical University, 127 Youyi Xilu, Xi’an, 710072, People’s Republic of China

    AiRong Qian, Wei Zhang, YuanYuan Weng & Peng Shang

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  1. AiRong Qian
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  2. Wei Zhang
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  3. YuanYuan Weng
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  4. Peng Shang
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Correspondence to Peng Shang.

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Qian, A., Zhang, W., Weng, Y. et al. Stealth siRNA against CD147 inhibits hepatocellular carcinoma cell metastatic properties. Biologia 63, 756–763 (2008). https://doi.org/10.2478/s11756-008-0132-x

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  • DOI: https://doi.org/10.2478/s11756-008-0132-x

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