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SIRT6 abrogation promotes adrenocortical carcinoma through activation of NF-κB signaling

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Abstract

As an uncommon malignancy in the adrenal gland, adrenocortical carcinoma (ACC) is characterized by thorny diagnosis and poor clinical outcome, necessitating innovative treatment strategies. Sirtuin 6 (SIRT6), a tumor suppressor, modulates aerobic glycolysis of malignant cells and has an impact on tumorigenesis. This study focused on investigating SIRT6 expression in ACC and how it generates cancer phenotypes. SIRT6 expression was inhibited in ACC tissues according to western blotting, real-time polymerase chain reaction, and immunohistochemistry. MTT assay, TUNEL assay, and flow cytometry were performed to evaluate the contribution of SIRT6 to cell invasion, proliferation, death, and migration. It was shown that SIRT6 knockdown promoted cell invasion, proliferation, and migration, and inhibited cell death. Moreover, it was found that SIRT6 knockdown upregulated TLR4 and reinforced phosphorylation of the nuclear transcription factor-kappa B (NF-κB) subunit p65 as well as inhibitor of nuclear factor kappa-B kinase. Additionally, SIRT6 knockdown significantly enhanced expression of calcitonin gene-related peptide as well as transient receptor potential vanilloid subtype 1. It also reinforced reactive oxygen species generation. Overall, our research findings demonstrate that SIRT6 serves as a tumor suppressor via regulation of the NF-κB pathway, which could offer an innovative strategy to treat ACC.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Chengdu, 610041, Sichuan, China

    Xueyi Wu & Haoming Tian

  2. Department of Intensive Medicine, Women and Children’s Hospital of Sichuan Province, Chengdu, 610043, China

    Long Xue

  3. Department of Eugenics, Women and Children’s Hospital of Sichuan Province, Chengdu, 610043, China

    Lizhi Wang

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  1. Xueyi Wu
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  2. Haoming Tian
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  3. Long Xue
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  4. Lizhi Wang
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Correspondence to Haoming Tian.

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This study has been approved by the Ethics Committee of the West China Hospital, Sichuan University.

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Wu, X., Tian, H., Xue, L. et al. SIRT6 abrogation promotes adrenocortical carcinoma through activation of NF-κB signaling. Mol Cell Biochem 458, 1–10 (2019). https://doi.org/10.1007/s11010-019-03525-8

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