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Aberrant upregulation of LRRC1 contributes to human hepatocellular carcinoma

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Abstract

Loss of apico-basal polarity often results in a malignant phenotype in epithelial tissues. Aberrant expression of polarity mediator proteins is closely associated with this process. LRRC1/LANO, a putative cell polarity regulator, was previously screened from our gene expression profiling in which its expression was significantly upregulated in hepatocellular carcinoma (HCC). In the present study, we provide evidences that LRRC1 plays a potential oncogenic function in HCC. Consistent with the microarray data, quantitative real-time PCR results showed LRRC1 was aberrantly upregulated in 37/56 (66.1 %, more than twofolds) of HCC specimens compared with adjacent non-cancerous livers. Furthermore, the cellular expression of LRRC1 in all HCC cell lines examined exhibited much higher level than that in normal adult liver tissue. Functional analyses revealed that overexpression of LRRC1 promoted, while knockdown of LRRC1 by RNA interference inhibited the growth and colony formation of HCC cells. Importantly, enhanced expression of LRRC1 conferred NIH3T3 cells the ability of cell transformation. In a xenograft tumor model, we found LRRC1 overexpression increased the tumorigenicity of HCC cells. Thus, our collective findings suggest that LRRC1 contributes to HCC development, and may be a potential target for therapeutic intervention in this disease.

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Acknowledgments

This work was supported by grants from the Chinese National Key Projects for Infectious Disease (2012ZX10002012-008) and Chinese National Key Program on Basic Research (973 Program) (2010CB529204 and 2010CB529206).

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The authors have declared that no conflict of interest exists.

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Authors and Affiliations

  1. Key Laboratory of Systems Biomedicine (Ministry of Education) of Rui-Jin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui-Jin II Road, Shanghai, 200025, China

    Yandong Li, Bo Zhou, Ruifang Liu & Ze-Guang Han

  2. Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, 351 Guo Shou-Jing Road, Shanghai, 201203, China

    Yandong Li, Bo Zhou, Jihong Dai, Ruifang Liu & Ze-Guang Han

  3. Translational Medicine Research Center, Shanghai East Hospital, Tongji University School of Medicine, 150 Ji-Mo Road, Shanghai, 200120, China

    Yandong Li

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  1. Yandong Li
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Correspondence to Ze-Guang Han.

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Li, Y., Zhou, B., Dai, J. et al. Aberrant upregulation of LRRC1 contributes to human hepatocellular carcinoma. Mol Biol Rep 40, 4543–4551 (2013). https://doi.org/10.1007/s11033-013-2549-8

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