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

  • Xueyi Wu
  • Haoming TianEmail author
  • Long Xue
  • Lizhi Wang
Article

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.

Keywords

Sirtuin 6 Adrenocortical carcinoma NF-κB Transient receptor potential vanilloid Calcitonin gene-related peptide Reactive oxygen species 

Notes

Funding

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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Endocrinology and Metabolism, West China HospitalSichuan UniversityChengduChina
  2. 2.Department of Intensive MedicineWomen and Children’s Hospital of Sichuan ProvinceChengduChina
  3. 3.Department of EugenicsWomen and Children’s Hospital of Sichuan ProvinceChengduChina

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