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.

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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