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B7-H4 facilitates proliferation and metastasis of colorectal carcinoma cell through PI3K/Akt/mTOR signaling pathway

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Abstract

B7-H4 is over-expressed in various tumors and may affect many aspects of cancer biology. Our previous studies have reported that the over-expressed B7-H4 in serum or tumor tissue of colorectal carcinoma (CRC) patients was closely related to CRC progression. However, B7-H4 in cell biological characteristics of CRC is not well studied. Here, we investigate the effect of the B7-H4 on cell proliferation, migration and its expression regulated by PI3K/Akt/mTOR signaling pathway in CRC. Firstly, pSilencer 4.1-B7-H4-shRNA vector was constructed and stable transfection was performed on HT-29 cells. Secondly, cell proliferation, cell cycle, cell apoptosis and cell migration were evaluated after B7-H4 silencing, and the expression of Bcl-2, caspase-3, MMP-2 and MMP-9 was also measured. Finally, the regulation of B7-H4 by PI3K/Akt/mTOR signaling pathway was measured followed by treatment with or without PI3K/Akt and mTOR inhibitor. The results showed that the viability of HT-29 cells was significantly decreased after B7-H4 silencing (P < 0.05). B7-H4 silencing significantly increased the apoptosis rate and caspase-3 protein expression while decreased Bcl-2 protein expression (P all < 0.05). B7-H4 silencing also significantly reduced the migration of HT-29 cells (P < 0.01) and the secretion of MMP-2 or MMP-9 (P all < 0.05). Following treatment with PI3K/Akt and mTOR inhibitor in HT-29 cells, the expression of B7-H4 was significantly downregulated compared with untreated group (P all < 0.05). Our results strongly suggest that B7-H4 may be involved in cell proliferation and migration by PI3K/Akt/mTOR signaling pathway. Therefore, blocking B7-H4 signaling might be a novel treatment strategy for CRC.

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Acknowledgments

This research was supported by the Science and Technology Department of Jilin province (20170414030GH; 20190201220JC) and the Education Department of Jilin Province (JJKH20180353 KJ).

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  1. Chun Li and Yudong Zhan have contributed equally to this paper.

Authors and Affiliations

  1. Department of Pathology, Beihua University Faculty of Medicine, No. 3999 Binjiang East Road, Jilin, 132013, Jilin, People’s Republic of China

    Chun Li, Yudong Zhan, Xuzhe Ma, Hui Fang & Xiaodong Gai

  2. Department of Pathology, Jingmen No. 1 People’s Hospital, Jingmen, 448000, Hubei, People’s Republic of China

    Yudong Zhan

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  1. Chun Li
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Correspondence to Xiaodong Gai.

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This study was conducted in accordance with the approved institutional guidelines of Beihua University in China. The Ethics Committee of Beihua University (2018015) approved this study and all experimental protocols.

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Li, C., Zhan, Y., Ma, X. et al. B7-H4 facilitates proliferation and metastasis of colorectal carcinoma cell through PI3K/Akt/mTOR signaling pathway. Clin Exp Med 20, 79–86 (2020). https://doi.org/10.1007/s10238-019-00590-7

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  • DOI: https://doi.org/10.1007/s10238-019-00590-7

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