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BCL11B regulates MICA/B-mediated immune response by acting as a competitive endogenous RNA

Oncogene volume 39, pages 1514–1526 (2020)Cite this article

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Abstract

Cancer immune surveillance is an important host protection process that inhibits carcinogenesis and maintains cellular homeostasis. The major histocompatibility complex class I-related molecules A and B (MICA and MICB) are NKG2D ligands that play important roles in tumor immune surveillance. In the present study, by a combined bioinformatics prediction and experimental approach, we identify BCL11B 3′-UTR as a putative MICA and MICB ceRNA. We demonstrate in several human cell lines of different origins that the knockdown of BCL11B downregulates surface expression of MICA and MICB. Furthermore, we demonstrate miRNA dependency of BCL11B-mediated MICA and MICB regulation in Dicer knockdown HCT116 cells. In addition, MICA/B-targeting miRNAs (miR-17, miR-93, miR-20a, miR-20b, miR-106a, and miR-106b) repressed the expression of BCL11B by targeting its 3′-UTR. Moreover, we showed that the BCL11B knockdown-mediated downregulation of MICA/B resulted in reduced NK cell elimination in vitro and in vivo through reduced recognition of NKG2D. Of particular significance, BCL11B displays tumor-suppressive properties. The expression of BCL11B is downregulated in colon cancer tissues and associated with a reduced median survival of colon cancer patients. Taken together, our study revealed a new mechanism of BCL11B that prevents immune evasion of cancerous cells by upregulation of the NKG2D ligands MICA and MICB in a ceRNA manner.

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Acknowledgements

This work was supported by National Natural Sciences Foundation of China (grant NSFC-81472651, 81201589).

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  1. These authors contributed equally: Mengyao Qian, Jingwen Geng, Kaili Luo

Authors and Affiliations

  1. Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, PR China

    Mengyao Qian, Jingwen Geng, Kaili Luo, Zheng Huang, Qinkai Zhang, Liying Ji & Jianmin Wu

  2. Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, PR China

    Jian-an Zhang

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Qian, M., Geng, J., Luo, K. et al. BCL11B regulates MICA/B-mediated immune response by acting as a competitive endogenous RNA. Oncogene 39, 1514–1526 (2020). https://doi.org/10.1038/s41388-019-1083-0

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