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SERPINA3 Silencing Inhibits the Migration, Invasion, and Liver Metastasis of Colon Cancer Cells

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Abstract

Objective

To investigate the impact of SERPINA3 on the migration, invasion, and liver metastasis of colon cancer cells.

Methods

Immunohistochemical staining was conducted to determine SERPINA3 expression in the cancer and adjacent normal tissues of 131 patients suffering from colon cancer. In vitro experiment, colon cancer cells with low (HT-29P), intermediate (KM-12C), and high (HT-29LMM, KM-12L4) metastatic potential were obtained to examine SERPINA3 expression levels. Besides, quantitative real-time PCR (qRT-PCR) and Western Blot were performed to detect SERPINA3 expression in HT-29LMM and KM-12L4 cells transfected with SERPINA3 siRNA; Wound-healing and Transwell assays to measure cell migration and invasion, respectively; and ELISA to detect MMP-2 and MMP-9 levels. In vivo experiment, mice with liver metastasis of colon cancer were established to observe the effect of SERPINA3 silencing on liver metastasis. Immunohistochemical assay was applied to evaluate the expressions of Serpina3, Mmp-2, Mmp-9, and proliferating cell nuclear antigen (Pcna) in liver metastasis tissues.

Results

SERPINA3 in colon cancer tissues was higher than in adjacent normal tissues, which was associated with patients’ clinicopathological features. Besides, SERPINA3 expression showed a rising trend in low, intermediate, and high metastatic potential colon cancer cells. After KM-12L4 and HT-29LMM cells transfected with SERPINA3 siRNA, the migration and invasive ability of cells, as well as the expression levels of MMP-2 and MMP-9 were all decreased. Moreover, SERPINA3 siRNA could not only reduce live metastasis of mice, but also down-regulate the expression of Mmp-2 and Mmp-9 in liver metastasis tissues.

Conclusion

SERPINA3 silencing could inhibit the migration, invasion, and liver metastasis of colon cancer cells.

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Acknowledgments

The authors like to appreciate the reviewers for their helpful and instructive comments on this article.

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Author notes

  1. Long-Lei Cao and Xu-Feng Pei have contributed equally to this study and share first authorship.

Authors and Affiliations

  1. Department of Anal-colorectal Surgery, Jingzhou Central Hospital, the Second Clinical Medical College, Yangtze University, Renmin Road 1, Jingzhou, 434020, China

    Long-Lei Cao, Jie Yu, Hui Ye, Chang-Lei Xi, Pei-Yun Wang & Zhi-Lin Gong

  2. Department of Emergency Surgery, Jingzhou Central Hospital, the Second Clinical Medical College, Yangtze University, Jingzhou, 434020, China

    Xu-Feng Pei

  3. Department of Gastroenterology, Jingzhou Central Hospital, the Second Clinical Medical College, Yangtze University, Jingzhou, 434020, China

    Xu Qiao

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  1. Long-Lei Cao
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Correspondence to Zhi-Lin Gong.

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Cao, LL., Pei, XF., Qiao, X. et al. SERPINA3 Silencing Inhibits the Migration, Invasion, and Liver Metastasis of Colon Cancer Cells. Dig Dis Sci 63, 2309–2319 (2018). https://doi.org/10.1007/s10620-018-5137-x

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  • DOI: https://doi.org/10.1007/s10620-018-5137-x

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