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Primary Culture of Rat Adrenocortical Cells and Assays of Steroidogenic Functions
Published on: March 12, 2019
SIRT6 abrogation promotes adrenocortical carcinoma through activation of NF-κB signaling
Xueyi Wu1, Haoming Tian2, Long Xue3
1Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Chengdu, 610041, Sichuan, China.
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.
Insights
Sirtuin 6 (SIRT6) acts as a tumor suppressor in adrenocortical carcinoma (ACC). Inhibiting SIRT6 promotes cancer cell invasion and proliferation by activating the NF-κB pathway, suggesting SIRT6 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis, requiring novel treatments.
- Sirtuin 6 (SIRT6) is a tumor suppressor involved in regulating cancer cell metabolism and tumorigenesis.
Purpose of the Study:
- To investigate SIRT6 expression in ACC tissues.
- To elucidate the role of SIRT6 in generating cancer phenotypes in ACC.
Main Methods:
- Western blotting, real-time PCR, and immunohistochemistry were used to assess SIRT6 expression.
- MTT assay, TUNEL assay, and flow cytometry evaluated SIRT6's impact on cell invasion, proliferation, and death.
- Analysis of downstream signaling pathways including NF-κB, TLR4, CGRP, TRPV1, and reactive oxygen species.
Main Results:
- SIRT6 expression was found to be inhibited in ACC tissues.
- SIRT6 knockdown promoted cell invasion, proliferation, and migration while inhibiting cell death.
- Knockdown of SIRT6 upregulated TLR4, enhanced NF-κB pathway activation, and increased reactive oxygen species generation.
Conclusions:
- SIRT6 functions as a tumor suppressor in ACC by regulating the NF-κB pathway.
- Targeting SIRT6 may offer a novel therapeutic strategy for treating adrenocortical carcinoma.
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