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B7-H3, Negatively Regulated by miR-128, Promotes Colorectal Cancer Cell Proliferation and Migration

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Abstract

Background

B7 homolog 3 (B7-H3), a member of the immunoregulatory ligand B7 family, is pivotal in T-cell-mediated immune response. It is widely expressed in diverse human tumors and its high expression indicates the poor prognosis of the patients. Nonetheless, B7-H3’s role in colorectal cancer (CRC) needs to be further explored.

Methods

Western blot and immunohistochemistry were employed for detecting B7-H3 protein expression in CRC tissues and cell lines, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized for detecting B7-H3 mRNA and miR-128 expression levels. CRC cell lines SW620 and HT29 were used to construct B7-H3 overexpression or knockdown cell models, respectively. Cell counting kit-8 (CCK-8), 5-bromo-2′-deoxyuridine (BrdU), and scratch wound healing assays were employed for evaluating the effects of B7-H3 on CRC cell multiplication and migration. Besides, the regulatory relationship between miR-128 and B7-H3 was validated through dual-luciferase reporter gene assay, qRT-PCR, and western blotting.

Results

B7-H3 expression level was remarkably elevated in CRC tissues and cell lines, and its high expression level was associated with increased tumor size, positive lymph node metastasis, and increased T stage. In CRC cells, B7-H3 overexpression significantly facilitated the cell multiplication and migration, while B7-H3 knockdown worked oppositely. Moreover, B7-H3 was identified as a target of miR-128, and miR-128 negatively regulated B7-H3 expression in CRC cells.

Conclusion

B7-H3 expression is upregulated in CRC tissues and cell lines, and B7-H3 participates in promoting the proliferation and migration of CRC cells. Besides, B7-H3 expression is negatively regulated by miR-128 in CRC.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

References

  1. DeSantis, C. E., Lin, C. C., Mariotto, A. B., Siegel, R. L., Stein, K. D., & Kramer, J. L., et al. (2014). Cancer treatment and survivorship statistics, 2014. CA: A Cancer Journal for Clinicians, 64(4 Jul–Aug), 252–271.

    Google Scholar 

  2. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6 Nov), 394–424.

    Google Scholar 

  3. Kuipers, E. J., Grady, W. M., Lieberman, D., Seufferlein, T., Sung, J. J., & Boelens, P. G., et al. (2015). Colorectal cancer. Nature Review Disease Primers, 1(Nov), 15065.

    Article  Google Scholar 

  4. Martini, G., Troiani, T., Cardone, C., Vitiello, P., Sforza, V., & Ciardiello, D., et al. (2017). Present and future of metastatic colorectal cancer treatment: a review of new candidate targets. World Journal of Gastroenterology, 23(26 Jul), 4675–4688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Collins, M., Ling, V., & Carreno, B. M. (2005). The B7 family of immune-regulatory ligands. Genome Biology, 6(6), 223.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Hansen, J. D., Du Pasquier, L., Lefranc, M. P., Lopez, V., Benmansour, A., & Boudinot, P. (2009). The B7 family of immunoregulatory receptors: a comparative and evolutionary perspective. Molecular Immunology, 46(3 Jan), 457–472.

    Article  CAS  PubMed  Google Scholar 

  7. Sun, X., Vale, M., Leung, E., Kanwar, J. R., Gupta, R., & Krissansen, G. W. (2003). Mouse B7-H3 induces antitumor immunity. Gene Therapy, 10(20 Sep), 1728–1734.

    Article  CAS  PubMed  Google Scholar 

  8. Ling, V., Wu, P. W., Spaulding, V., Kieleczawa, J., Luxenberg, D., & Carreno, B. M., et al. (2003). Duplication of primate and rodent B7-H3 immunoglobulin V- and C-like domains: divergent history of functional redundancy and exon loss. Genomics, 82(3 Sep), 365–377.

    Article  CAS  PubMed  Google Scholar 

  9. Hasselbalch, H. C. (2012). Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer? Blood, 119(14 Apr), 3219–3225.

    Article  CAS  PubMed  Google Scholar 

  10. Ingebrigtsen, V. A., & Boye, K. (2014). B7-H3 expression in colorectal cancer: associations with clinicopathological parameters and patient outcome. BMC Cancer, 14(Aug), 602.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Jiang, B., Zhang, T., Liu, F., Sun, Z., Shi, H., & Hua, D., et al. (2016). The co-stimulatory molecule B7-H3 promotes the epithelial-mesenchymal transition in colorectal cancer. Oncotarget, 7(22 May), 31755–31771.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Xue, J., Niu, J., Wu, J., & Wu, Z. H. (2014). MicroRNAs in cancer therapeutic response: friend and foe. World Journal of Clinical Oncology, 5(4 Oct), 730–743.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Friedman, R. C., Farh, K. K., Burge, C. B., & Bartel, D. P. (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome Research, 19(1 Jan), 92–105.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Li, L., Wang, X., Li, W., Yang, L., Liu, R. & Zeng, R. et al.(2018). miR-21 modulates prostaglandin signaling and promotes gastric tumorigenesis by targeting 15-PGDH. Biochemical and Biophysical Research Communications, 495(1 Jan), 928–934.

    Article  CAS  PubMed  Google Scholar 

  15. Yao, R., Xu, L., Wei, B., Qian, Z., Wang, J., & Hui, H., et al. (2019). miR-142-5p regulates pancreatic cancer cell proliferation and apoptosis by regulation of RAP1A. Pathology, Research and Practice, 215(6 Jun), 152416.

    Article  CAS  PubMed  Google Scholar 

  16. Zhou, T., Wu, L., Wang, Q., Jiang, Z., Li, Y., & Ma, N., et al. (2018). MicroRNA-128 targeting RPN2 inhibits cell proliferation and migration through the Akt-p53-cyclin pathway in colorectal cancer cells. Oncology Letters, 16(6 Dec), 6940–6949.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhou, Y. H., Chen, Y. J., Ma, Z. Y., Xu, L., Wang, Q., & Zhang, G. B., et al. (2007). 4IgB7-H3 is the major isoform expressed on immunocytes as well as malignant cells. Tissue Antigens, 70(2 Aug), 96–104.

    Article  CAS  PubMed  Google Scholar 

  18. Prasad, D. V., Nguyen, T., Li, Z., Yang, Y., Duong, J., & Wang, Y., et al. (2004). Murine B7-H3 is a negative regulator of T cells. The Journal of Immunology, 173(4 Aug), 2500–2506.

    Article  CAS  PubMed  Google Scholar 

  19. Suh, W. K., Gajewska, B. U., Okada, H., Gronski, M. A., Bertram, E. M., & Dawicki, W., et al. (2003). The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses. Nature Immunology, 4(9 Sep), 899–906.

    Article  CAS  PubMed  Google Scholar 

  20. Liu, Z., Zhang, W., Phillips, J. B., Arora, R., McClellan, S., & Li, J., et al. (2019). Immunoregulatory protein B7-H3 regulates cancer stem cell enrichment and drug resistance through MVP-mediated MEK activation. Oncogene, 38(1 Jan), 88–102.

    Article  CAS  PubMed  Google Scholar 

  21. Zhao, J., Meng, Z., Xie, C., Yang, C., Liu, Z., & Wu, S., et al. (2019). B7-H3 is regulated by BRD4 and promotes TLR4 expression in pancreatic ductal adenocarcinoma. The International Journal of Biochemistry & Cell Biology, 108(Mar), 84–91.

    Article  CAS  Google Scholar 

  22. Jiang, B., Liu, F., Liu, Z., Zhang, T., & Hua, D. (2016). B7-H3 increases thymidylate synthase expression via the PI3k-Akt pathway. Tumour Biology, 37(7 Jul), 9465–9472.

    Article  CAS  PubMed  Google Scholar 

  23. Zhang, T., Jiang, B., Zou, S. T., Liu, F., & Hua, D. (2015). Overexpression of B7-H3 augments anti-apoptosis of colorectal cancer cells by Jak2-STAT3. World Journal of Gastroenterology, 21(6 Feb), 1804–1813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Han, H., Wang, L., Xu, J., & Wang, A. (2018). miR-128 induces pancreas cancer cell apoptosis by targeting MDM4. Experimental and Therapeutic Medicine, 15(6 Jun), 5017–5022.

    PubMed  PubMed Central  Google Scholar 

  25. Zhao, J., Li, D., & Fang, L. (2019). MiR-128-3p suppresses breast cancer cellular progression via targeting LIMK1. Biomedicine & Pharmacotherapy, 115(Jul), 108947.

    Article  CAS  Google Scholar 

  26. Lian, B., Yang, D., Liu, Y., Shi, G., Li, J., & Yan, X., et al. (2018). miR-128 targets the SIRT1/ROS/DR5 pathway to sensitize colorectal cancer to TRAIL-induced apoptosis. Cellular Physiology and Biochemistry, 49(6), 2151–2162.

    Article  CAS  PubMed  Google Scholar 

  27. Wu, L., Shi, B., Huang, K., & Fan, G. (2015). MicroRNA-128 suppresses cell growth and metastasis in colorectal carcinoma by targeting IRS1. Oncology Reports, 34(5 Nov), 2797–2805.

    Article  CAS  PubMed  Google Scholar 

  28. Liu, T., Zhang, X., Du, L., Wang, Y., Liu, X., & Tian, H., et al. (2019). Exosome-transmitted miR-128-3p increase chemosensitivity of oxaliplatin-resistant colorectal cancer. Molecular Cancer, 18(1 Mar), 43.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Wang, L., Kang, F. B., Sun, N., Wang, J., Chen, W., & Li, D., et al. (2016). The tumor suppressor miR-124 inhibits cell proliferation and invasion by targeting B7-H3 in osteosarcoma. Tumour Biology, 37(11 Nov), 14939–14947.

    Article  CAS  PubMed  Google Scholar 

  30. Zhu, X. W., Wang, J., Zhu, M. X., Wang, Y. F., Yang, S. Y., & Ke, X. Y. (2019). MicroRNA-506 inhibits the proliferation and invasion of mantle cell lymphoma cells by targeting B7H3. Biochemical and Biophysical Research Communications, 508(4 Jan), 1067–1073.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Hubei Yican Health Industry Co., Ltd. for its linguistic assistance during the preparation of this manuscript.

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Author notes

  1. These authors contributed equally: Xiaomao Hu, Minxian Xu

Authors and Affiliations

  1. Department of Oncology, Affiliated Hospital of Xiangnan University, Chenzhou, 423000, Hunan, China

    Xiaomao Hu, Minxian Xu & Na Li

  2. Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, China

    Xiaomao Hu

  3. Department of Gastroenterology Surgery, Affiliated Hospital of Xiangnan University, Chenzhou, 423000, Hunan, China

    Yangzhi Hu

  4. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Lei Zhou

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  1. Xiaomao Hu
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Correspondence to Xiaomao Hu or Lei Zhou.

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Our study was approved by the Ethics Review Board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

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Hu, X., Xu, M., Hu, Y. et al. B7-H3, Negatively Regulated by miR-128, Promotes Colorectal Cancer Cell Proliferation and Migration. Cell Biochem Biophys 79, 397–405 (2021). https://doi.org/10.1007/s12013-021-00975-0

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  • DOI: https://doi.org/10.1007/s12013-021-00975-0

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