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TRIM37 overexpression is associated with chemoresistance in hepatocellular carcinoma via activating the AKT signaling pathway

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Abstract

Background

Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the worldwide. Sorafenib is approved for first-line therapy against advanced HCC, but chemo-resistance is still a leading cause of tumor relapse and treatment failure in HCC. Thus, there is a significant clinical need to identify effective strategies to overcome drug resistance on the disease.

Methods

The protein and mRNA expression of TRIM37 in HCC cell lines and patient tissues were determined using Real-time PCR and Western blot, respectively. HCC tissue samples were analyzed by IHC to investigate the association between TRIM37expression and the clinicopathological characteristics of HCC patients. Functional assays, such as MTT, FACS, and Tunel assay, are used to determine the oncogenic role of TRIM37 in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of TRIM37promotes chemoresistance in HCC.

Results

We found that both the mRNA and protein expression of TRIM37 was markedly upregulated in HCC cell lines and tissues, especially in Sorafenib-resistance HCC tissues. Moreover, high TRIM37 expression was associated with poor prognosis with HCC patients. TRIM37 overexpression confers Sorafenib resistance on HCC cells; however, inhibition of TRIM37 sensitized HCC cell lines to Sorafenib cytotoxicity. Additionally, TRIM37 upregulated the levels of AKT activity and phosphorylated AKT, thereby activating canonical AKT signaling.

Conclusion

Our findings suggest that targeting TRIM37 signaling may represent a promising strategy to enhance Sorafenib response in HCC patients with chemoresistant.

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Acknowledgment

Natural Science Foundation of China (No. 81602701, No.81974443); Natural Science Foundation of Guangdong Province (No. 2017A030313547, No. 2018A030313176); Science and Technology Projects Foundation of Guangdong Province (No. 2015A070710006, No. 2016A020215053); Science and Technology Projects Foundation of Guangzhou City (No. 201507020037, No. 201607010260); Research project of Gannan Medical University, Gannan Medical University Key Cultivation project (No:ZD201802); Natural Science Foundation of Jiangxi Province (No:20202BAB206040)

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Author notes

  1. Guosheng Tan and Binhui Xie contributed equally to the work.

Authors and Affiliations

  1. Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Guosheng Tan, Na Yu & Fangzeng Lin

  2. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China

    Binhui Xie

  3. Department of Radiotherapy, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Jianwen Huang

  4. Department of Nuclear Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Bing Zhang

  5. Department of Medical Oncology of the Eastern Hospital, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Heping Li

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  1. Guosheng Tan
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Correspondence to Heping Li.

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Tan, G., Xie, B., Yu, N. et al. TRIM37 overexpression is associated with chemoresistance in hepatocellular carcinoma via activating the AKT signaling pathway. Int J Clin Oncol 26, 532–542 (2021). https://doi.org/10.1007/s10147-020-01832-5

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  • DOI: https://doi.org/10.1007/s10147-020-01832-5

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