Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Chengdu, 610041, Sichuan, China.
Department of Intensive Medicine, Women and Children's Hospital of Sichuan Province, Chengdu, 610043, China.
Mol Cell Biochem. 2019 Aug;458(1-2):1-10. doi: 10.1007/s11010-019-03525-8. Epub 2019 Apr 15.
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.
作为肾上腺中一种罕见的恶性肿瘤，肾上腺皮质癌（adrenocortical carcinoma，ACC）的诊断困难且临床预后较差，需要创新的治疗策略。Sirtuin 6（SIRT6）作为一种肿瘤抑制因子，调节恶性细胞的有氧糖酵解，对肿瘤发生有影响。本研究旨在探讨 SIRT6 在 ACC 中的表达及其产生癌症表型的机制。通过 Western blot、实时聚合酶链反应和免疫组织化学检测，抑制 ACC 组织中的 SIRT6 表达。通过 MTT 检测、TUNEL 检测和流式细胞术评估 SIRT6 对细胞侵袭、增殖、死亡和迁移的影响。结果表明，SIRT6 敲低促进了细胞侵袭、增殖和迁移，抑制了细胞死亡。此外，还发现 SIRT6 敲低上调了 TLR4，并增强了核转录因子-κB（nuclear transcription factor-kappa B，NF-κB）亚基 p65 和 NF-κB 激酶抑制剂的磷酸化。此外，SIRT6 敲低还显著增强了降钙素基因相关肽和瞬时受体电位香草酸亚型 1 的表达，并增强了活性氧的产生。综上所述，我们的研究结果表明，SIRT6 通过调节 NF-κB 通路发挥肿瘤抑制作用，为治疗 ACC 提供了一种创新策略。
