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miR-19a promotes colitis-associated colorectal cancer by regulating tumor necrosis factor alpha-induced protein 3-NF-κB feedback loops

Oncogene volume 36, pages 3240–3251 (2017)Cite this article

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Abstract

Chronic inflammation is believed to have a crucial role in colon cancer development. MicroRNA (miRNA) deregulation is common in human colorectal cancers, but little is known regarding whether miRNA drives tumor progression by regulating inflammation. Here, we showed that miR-19a can promote colitis and colitis-associated colon cancer (CAC) development using a CAC mouse model and an acute colitis mouse model. Tumor necrosis factor-α (TNF-α) stimulation can increase miR-19a expression, and upregulated miR-19a can in turn activate nuclear factor (NF)-κB signaling and TNF-α production by targeting TNF alpha-induced protein 3 (TNFAIP3). miR-19a inhibition can also alleviate CAC in vivo. Moreover, the regulatory effects of miR-19a on TNFAIP3 and NF-κB signaling were confirmed using tumor samples from patients with colon cancer. These new findings demonstrate that miR-19a has a direct role in upregulating NF-κB signaling and that miR-19a has roles in inflammation and CAC.

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Acknowledgements

This work was partially supported by grants from the National Natural Science Foundation of China (81572354, 81571800, and 81371680) and Natural Science Foundation of Jiangsu Province (BK20161400).

Author contributions

Conceived and designed the experiments: TW, SS and YH. Performed the experiments: TW, XX, QX, JR, SS, CF and YH. Analyzed the data: TW, XX and SS. Wrote the paper: TW and YH.

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Authors and Affiliations

  1. Division of Immunology, The State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing, China

    T Wang, Q Xu, J Ren, S Shen & Y Hou

  2. Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China

    T Wang, S Shen & Y Hou

  3. Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    T Wang

  4. General Surgery, Jinling Hospital, Medical School, Nanjing University, Nanjing, China

    X Xu & C Fan

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Correspondence to S Shen, C Fan or Y Hou.

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Wang, T., Xu, X., Xu, Q. et al. miR-19a promotes colitis-associated colorectal cancer by regulating tumor necrosis factor alpha-induced protein 3-NF-κB feedback loops. Oncogene 36, 3240–3251 (2017). https://doi.org/10.1038/onc.2016.468

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