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TRIM31 is upregulated in hepatocellular carcinoma and promotes disease progression by inducing ubiquitination of TSC1–TSC2 complex

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Abstract

Tripartite motif (TRIM) 31 is a member of the tripartite motif-containing protein family, and TRIM family proteins are involved in a broad range of biological and pathological processes. However, the role of TRIM31 in hepatocellular carcinoma (HCC) progression is not known. Here we demonstrated that TRIM31 expression was significantly upregulated in liver cancer tissues compared with paired distal non-cancerous liver tissues from HCC patients, and its overexpression was significantly correlated with advanced disease status. Both gain and loss of function assay verified that TRIM31 promoted the malignant behaviors of HCC cells through overactivation of mammalian target of rapamycin complex1 (mTORC1) pathway. We further demonstrated that TRIM31 exerted its oncogenic effect by directly interacting with the tuberous sclerosis complex (TSC) 1 and TSC2 complex, the upstream suppressor of mTORC1 pathway, and promoting the E3 ligase-mediated K48-linked ubiquitination and degradation of this complex. In conclusion, this study demonstrated TRIM31 could promote HCC progression by targeting TSC1–TSC2 complex for degradation and further overactivating mTORC1 pathway. Thus, it revealed a novel molecular mechanism of HCC progression and indicated a potential therapeutic strategy against HCC by targeting TRIM31.

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Acknowledgements

We thank Dr Brendan D Manning (Harvard University) and Dr Cheryl Lyn Walker (Texas A&M University) for providing the TSC1 and TSC2 plasmids. This study was supported by the National Natural Science Foundation of China (No. 81472269 and No. 81672391) and the Science and Technology Development Project of Shandong Province (No. 2015GSF118047).

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  1. P Guo and X Ma: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Shandong University School of Basic Medical Sciences, Jinan, 250012, China

    P Guo, X Ma, W Zhao, W Huai, Y Qiu, Y Zhang & L Han

  2. Department of Gastroenterology, Provincial Hospital Affiliated with Shandong University, Jinan, 250021, China

    T Li

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  1. P Guo
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Correspondence to L Han.

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Guo, P., Ma, X., Zhao, W. et al. TRIM31 is upregulated in hepatocellular carcinoma and promotes disease progression by inducing ubiquitination of TSC1–TSC2 complex. Oncogene 37, 478–488 (2018). https://doi.org/10.1038/onc.2017.349

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